The year is 2805 A.D. The Earth is a barren dystopia covered in what are literally mountains of trash, suffering from numerous sandstorms and torrential downpours. Over 700 years ago, the megaconglomerate corporation Buy n Large (BnL) finally assumed control of the planet's entire economy, including the government, and humanity spiraled into a state of mass consumerism, quickly covering the planet in garbage. In the year 2105, BnL CEO Shelby Forthright sponsored a five-year exodus from Earth into space aboard a fleet of BnL starliners, the most prominent of them was the Axiom, taking a luxury cruise while millions of WALL•E (Waste Allocation Load Lifter Earth-Class) units were left behind to compress the trash into small cubes with which they used to build colossal towers which would be incinerated by massive city block-wide sized incinerators as part of the proposed "Operation Cleanup". They were to then initiate "Operation Recolonize", returning to Earth after five years, which was believed to be enough time to clean the planet. This plan failed, however, and as Earth was deemed too toxic to re-inhabit, BnL had all the WALL•E units deactivated, but somehow missing one.

The last active WALL•E on Earth has continued the same routine each and every day for 700 years. Each morning he would wake up and recharge his solar cells before setting off to fulfill his directive of constructing trash towers with compressed cubes, then return to his truck, a large vehicle designed for carrying the WALL-Es over all terrains, to shut down for the night. But by this time, he has become sentient and developed a personality. To cope with the boredoms of doing the same thing every day, other than working with his trusty cockroach companion Hal, he has become extremely curious. Whenever he would find anything he finds interesting in the refuse (a Rubik's cube, a light bulb, a match lighter, etc.) he would place it in a BnL cooler and take it back to his truck at the end of the day, placing it in his ever-growing knick-knack collection. He would also salvage spare parts for himself from his fellow deactivated WALL•E units should the worst happen. The pride of his collection, a VHS copy of the film Hello, Dolly!, which has taught him how to dance as well as all of his emotions. He loves the film and its music so much that he plays the song "Put On Your Sunday Clothes" while he works, and when he watches the scene with the song "It Only Takes a Moment", he learns how to hold hands; however, because he has no one else to hold hands with, he becomes lonely.

One day, he discovers something unlike anything else he has seen: a seedling plant. Stricken by its beauty and delicate appearance, he carefully pots it in an old shoe. While returning home from work later that day, WALL•E notices a small red dot on the ground, and decides to chase after it, ending up in the middle of a clearing. It turns out that the dot is actually a tracking laser of a landing ship. WALL•E immediately burrows underground for safety when he is caught underneath the ship while its landing; when he emerges, he witnesses a small white pod emerging from the ship. The pod opens itself and moves, revealing a sleek, state-of-the-art feminine probe-droid, who immediately begins scanning the area as if searching for something. WALL•E is stunned by the elegant-looking robot and falls in love with her upon first sight, but is too timid to speak to her, especially when she demonstrates her unhesitating will to fire her arm cannon at any sudden movement. WALL•E's companion Hal decides to approach the probe out of curiosity, and she tries to shoot him, but when she finds that her target is a harmless cockroach, she shows signs of light-heartedness by playing with him. However, she is startled by WALL•E and holds him at a gunpoint, demanding to know who he is; Hal defends WALL•E by crawling into his hand. The probe scans him, subsequentially deeming him non-hostile returning to her mission, thinking nothing else of him. WALL•E, still fascinated by the probe, becomes determined to attract her attention as cautiously as possible, but she hardly notices him. Soon she begins to grow frustrated with not finding what she is looking for, but after taking her anger out on a cargo ship crane that she gets stuck to and destroys, she calms down. By now, WALL•E sums up the nerve to approach the probe while she is docile and speaks with her again, introducing himself. The probe, while refusing to disclose her classified "directive", becomes amused by his behavior, and formally introduces herself as "EVE". A sandstorm suddenly brews, and WALL•E directs EVE to his truck for shelter. EVE is fascinated when she sees all the little knick-knacks WALL•E has collected. Among his treasures, he shows her Hello, Dolly! and tries to teach her how to dance, though it gets a little out of hand and she accidentally knocks him away, damaging his right eye; fortunately, he is able to repair himself with a spare eyepiece. He tries to hold her hand as he had seen in the film, which he determines to be an act of sharing love. Unfortunately for him, EVE does not understand what he is trying to do and thus does not return his love, especially as she is distracted by the mesmerizing flame of a match lighter and does not fully appreciate the film as he does. WALL•E then decides to show her the plant he found; suddenly, EVE grows excited, takes the plant from him, and stores it inside herself, seals up into her pod form, and shuts down. WALL•E does not understand why she will not unlock or speak to him, but nonetheless does everything in his power to keep her motionless body safe from the elemental hazards of the desolate Earth in the hopes she will wake up, taking her out on a series of "dates" in the process; finally, WALL•E gives up hope that she will ever awaken and leaves to resume his work. Soon the ship EVE arrived in returns and takes her away. While it is clear that EVE had sent a homing beacon to her ship to collect her, WALL•E is unwilling to leave her and climbs onto the side of the ship, telling Hal to stay where he is, clinging on as it launches off the planet and into the depths of space. WALL•E gazes in wonder at the beautiful cosmos as he arrives aboard the Axiom.

Still deactivated, EVE is taken to a group of cleaning robots led by a small robot named M-O. WALL•E is also taken by accident, dumbfounding and irritating M-O with the amount of dirt on his body. The two robots engage in a brief, mild conflict about his filthy body when the ship's second-in-command, GO-4, inspects EVE and finds that she is storing the plant inside her, and he summons a transport cart robot called MVR•A to take him and EVE taken away somewhere, with WALL•E giving chase. As M-O prepares to leave for his next assignment, he notices that WALL•E has left an awful amount of filth behind by his tracks. M-O ultimately decides to forgo his assignment and clean these tracks on his own, knowing they will lead him to WALL•E, and obsessively initiates a cat-and-mouse chase while unknowingly developing the ability to think for himself. Around this time, WALL•E discovers that the humans aboard the vessel have lost considerable bone mass and are morbidly obese, having adapted after centuries of living in micro-gravity, consuming liquefied food, and leaving all manual labor to be handled by the robots. They never acknowledge each other in ways other than through holo-screens in front of their faces, and cannot even move without a Hover Chair or other automated assistance. Even piloting the ship is left in the care of the autopilot, aptly named "Auto"; the only thing that Captain really does is make the morning announcement each and every day, as well as re-check the ship's status with Auto. WALL•E encounters a human man named John who falls off his hoverchair after trying to give the cup to WALL•E, but is quickly helped back on by WALL•E, much to his appreciation. While trying to approach EVE's tram, he accidentally turns off the computer screen of another human, a woman named Mary, awakening her to the world around her, mainly the pool, which utterly amazes her.

EVE is taken to the Captain, who is suddenly surprised that she has returned "positive" (i.e., with a plant), and learns of Shelby Forthright's "Operation Recolonize"; all he needs to do now is bring the plant to the holo-detector on the lido deck, and the ship will automatically Hyperjump to Earth. EVE reactivates and finds WALL•E, telling him to stay hidden. But when the Captain prepares to take the plant, he finds that it is missing. EVE assumes that WALL•E took it, though he was never seen doing such a thing. Unable to find the plant anywhere, Auto declares that EVE's memory is faulty, and that things can go back to normal; the Captain similarly dismisses the event as a false alarm and has EVE sent to the repair ward for diagnosis. WALL•E is suddenly discovered, and he shakes hands with the Captain, getting dirt on his hand. The Captain has WALL•E taken with EVE to be cleaned. As they leave for the repair ward, EVE refuses to speak with or even look at WALL•E, believing that he had not only stolen, but also lost the plant, much to his dismay. The Captain analyzes the dirt WALL•E left and discovers that he is from Earth. His curiosity about humanity's former home planet is ultimately sparked, and he becomes enthralled in researching what it is like.

Arriving at the repair ward with all the other malfunctioning robots on the ship, EVE is fitted with a red boot that deactivates her with the press of a button. She is taken into a room behind a translucent screen as WALL•E is placed in a cell. Her laser arm is removed and she is cleaned, but while EVE actually enjoys the experience, WALL-E misinterprets it by what he can see and hear and believes she is being tortured. WALL•E escapes his cell and breaks into the diagnosis room, grabbing her detached arm and accidentally firing it at the power cell of the room, releasing the legitimately haywire robots from their cells; in the process, WALL•E accidentally begins playing "Put on Your Sunday Clothes". As WALL•E is whisked away by the malfunctioning robots, they are stopped by the stewards, allowing EVE to track WALL•E down. However, EVE is photographed by the stewards in a position that makes her appear as if she is going to attack with her laser, labeling her as a "rogue robot". Now a wanted criminal, EVE must evade security as she takes WALL•E to the escape pods. WALL•E and EVE in space around the Axiom. Furious and fed up with WALL•E for all the trouble he has caused for the ship and for her, EVE activates an escape pod set to return him to Earth. WALL•E wants EVE to come with him but she refuses, stating that she must stay to find the plant and fulfill her directive. Slightly offended, WALL•E stubbornly refuses to leave, frustrating EVE. They are then forced to hide when GO-4 enters the room and activates the pod's self-destruct sequence. He then places the plant inside, exposing himself as the true thief. WALL•E goes into the pod to retrieve the plant for EVE, but GO-4 launches it with him inside, and EVE, in spite of everything he had done, gives chase to try and save him. Realizing that he cannot stop the pod or its self-destruct sequence, WALL•E tries to make an escape by opening the emergency hatch, but it is stuck; as he begins banging on the door with a fire extinguisher, the pod explodes. Aghast, EVE rushes to the scene when WALL•E flies past her by completely unharmed, having managed to escape at the last second and find propulsion with the fire extinguisher. EVE is deeply relieved and happily reconciles with WALL•E, but before it even comes to her mind, WALL•E presents to her the plant, also unharmed. EVE is overjoyed and, after taking back the plant, gives WALL•E a "kiss", which causes a small static shock, and they share a dance in space around the Axiom. Witnessing this dance are the humans John and Mary, who recognize WALL•E and suddenly notice each other, when John accidentaly places his hand on Marys, falling in love.

WALL•E and EVE return onboard the Axiom where EVE and WALL•E are still wanted by security. WALL•E tries to hold her hand again, but EVE is much too concerned with carrying out her directive, as well as keeping a low profile, and rejects his offer. She decides to sneak onto the bridge through the garbage chute, telling WALL•E to stay put. She presents the plant to the Captain who, after being completely fascinated with the customs on Earth he had learned about, such as farming and dancing, decides to watch her security recordings of Earth; however, he is shocked and confused to see that Earth is not the green paradise he learned it to be. As they watch the recordings, EVE witnesses footage from the Hello, Dolly! video that WALL•E had shown her before. She watches the scene with "It Only Takes a Moment", which she did not previously appreciate, and learns how to hold hands much like WALL•E had. The recording then begins to play security footage of what happened when she took the plant and entered standby mode, and she sees everything that WALL•E did to protect her motionless body, as well as all the "dates" he took her on. She is touched by WALL•E's deeds and, realizing that he truly does love her, begins to fall in love with him as well. Meanwhile, WALL•E grows rather anxious about waiting for EVE, trying to put his feelings for her in the right words, until he decides to follow her, slowly climbing up the garbage chute.

The Captain has an epiphany: a great deal of care and work is needed in order to benefit Earth, and that humanity must return to make amends for their past mistakes and save it. He prepares to place the plant in the holo-detector, but Auto tries to take it from him, saying that they cannot return to Earth. Auto refuses to disclose why not, but the annoyed Captain orders him to reveal his intentions. Auto plays the recording of a top-secret announcement by Shelby Forthright, explaining how "Operation Cleanup" had failed and he deemed Earth too toxic to ever support life again. He issued Directive A-113, which was for autopilots to stay the course in space and never return to Earth. The Captain is outraged, learning that this video was taken over 700 years ago, and that things have now changed: if one plant can survive on Earth, then that certainly proves that Earth is now inhabitable. Looking at the images of the photos of the captains before, the Captain notices that Auto is in every one and is moving closer to the captains down the generations, meaning he has slowly been taking control. Deciding to officially take command, the Captain demands that Auto stand down. Auto, however, overrules this, being unable to disobey his directive, and stages a mutiny with GO-4, who steals the plant back for Auto. EVE tries to coerce GO-4 into returning it, but he throws it down the garbage chute. Fortunately, it conveniently lands on top of WALL•E's head as he arrives to be with EVE. GO-4 restrains EVE, and WALL•E and Auto have a brief struggle in which WALL•E stores the plant inside his chest cavity before Auto violently electrocutes him, sending him down the chute. He then deactivates the distressed EVE with her red boot and has her sent down the chute as well before proceeding to lock the Captain in his quarters.

EVE reactivates when the robotic mice on her body activate her boot. She finds herself stuck in a pile of garbage in the waste disposal facility, inhabited by a pair of giant WALL•A robots, which are much like WALL•E with the exception of size. She is trapped inside a large compressed garbage cube, her boot breaking off in the process, and placed in an airlock, set to be jettisoned into space with the seriously damaged WALL•E and the plant. While EVE frees herself from the trash and struggles to free WALL•E before the airlock doors close, M-O appears in the chamber, having followed WALL•E there while fixated on cleaning his filthy trail, and charges towards them. The doors close on M-O's head, keeping them open, but the airlock is activated. EVE, with WALL•E in her arm, clings onto M-O as they are being sucked into the vacuum of space. The WALL•As take notice and deactivate the airlock, saving them. As M-O quickly recovers from this traumutizing experience, finally cleaning as well as befriending WALL•E, EVE finds that WALL•E's encounter with Auto has burned a hole in his motherboard, and tries in vain to find replacement parts among the trash. WALL•E gives her the plant, telling her to bring it to the holo-detector and fulfill her directive, but EVE, now in love with him, refuses; she tosses the plant aside and declares that her new directive is to be with WALL•E, as she believes their love is all that matters. She offers to hold WALL•E's hand, but he rejects it and picks up the plant, insisting she return it, but EVE is rather indecisive. WALL•E consoles and reminds her that if they return the plant, they will return to Earth, where he had stockpiled spare parts for himself which can be used to repair him. EVE finally agrees and, with WALL•E, M-O and the plant in tow, they escape the facility, while the WALL•As wave goodbye.

EVE directly confronts the stewards and attacks, recognized as the "rogue robot" from before. The Captain views the new security photo from his quarters and notices that they have the plant. He hotwires the communications in his room, directing WALL•E and EVE to the holo-detector before being cut off by Auto. He then takes a holographic image of WALL•E holding the plant and presents it to Auto, tricking him into thinking he has obtained it. Auto enters his chambers where the Captain jumps him, engaging in a struggle that accidentally knocks GO-4 out of the bridge and crashing to the deck below. Meanwhile, WALL•E, EVE and M-O recruit the malfunctioning robots that were let loose, who recognize them thanks to the song "Put on Your Sunday Clothes" he had played earlier, and decide to help them by destroying the stewards that are in their way before reaching the lido deck, in return for WALL•E releasing them from the repair ward. The Captain manages to activate the holo-detector, which is a pedestal that rises from the deck, summoning all humans, asleep or awake, to the main chamber. But when all the humans are on the lido deck Auto sees EVE and WALL•E so he tilts the Axiom to its side, knocking the Captain to the ground, piling all the humans in a corner, and causing WALL•E and EVE to drop the plant. EVE protects the humans from falling trams that threaten to crush them;during the chaos, John and Mary save a group of babies sliding down the floor like the rest of them. Auto tries to close the holo-detector, but WALL•E attempts to hold it open. Auto then tries to kill WALL•E by slamming the holo-detector shut, which jams over his body and ultimately crushes him. As EVE is preoccupied with protecting the humans and forced to watch on in horror, the enraged Captain summons the strength to stand up on his own and resume his fight with Auto. He manages to relieve Auto of duty by switching to manual control, and rights the Axiom. EVE rushes to WALL•E's aid, retrieving the plant with the aid of the humans who also managed to stand up and the other robots. She places it in the holo-detector, opening it and releasing him, finding that he is mortally damaged. The plants origin is verified, the computer begins the countdown to hyperjump, and within 10 seconds the Axiom hyperjumps back to Earth.

EVE holds WALL•E's hand.After a few seconds in Hyperspace the Axiom drops out and speeds towards Earth and lands in its Launch/Landing site, EVE carries the dying WALL•E in her arms back to his truck where she frantically puts him back together with his surplus and recharges him, successfully reactivating him. Relieved, EVE proceeds to try and hold his hand like they desired so many times before, but WALL•E does not seem to recognize her, turning away and preparing to leave. EVE realizes that WALL•E has lost his memory after the incident but, in a state of blissful denial, does everything in her power to make him remember: she shows him his treasured knick-knacks as well as Hello, Dolly!, but WALL•E instead begins to compress his collection into cubes, following his original directive. In one final attempt, she tries to play WALL•E's recording of "It Only Takes a Moment" but finds that it too has been erased, and she concedes that the WALL•E she knew and loved is gone forever. Heartbroken, EVE finally takes a hold of his hand and softly hums "It Only Takes a Moment" herself before giving him a parting "kiss", causing another static shock. She prepares to leave in sorrow, but her fingers are stuck between his. Suddenly, WALL•E slowly grasps EVE's hand, his eyes readjust, and he recognizes her; the spark of the kiss had rebooted his memory, as the first one had left him lovestruck, so to speak. EVE is filled with joy, WALL•E is ecstatic that their hands are together, and they embrace for a tender kiss. The other robots, who had followed, were ushered away by M-O to give them some privacy. WALL•E and EVE prepare to spend the rest of their lives together alongside their new robot friends, and assisting the humans while they work to restore the Earth to its former glory; first starting by planting the little seedling in the ground.

Over the end credits, the restoration of Earth is depicted through pictures that evolve from rather primitive hieroglyphs to impressive paintings. As the years pass, Earth becomes as lush and green as ever, and humans have become active to the extent that they regain their former body structures. In the end, WALL•E and EVE are still together, and they observe a large tree;it is shown that this tree is the same plant that had brought them home many years before.