A rogue death sphere called the V-GINY, bent on censoring and destroying planets it deems to be indecent, is headed for Earth. Leela volunteers to destroy the death sphere, and reluctantly allows Zapp to come along. Their attack is disrupted and they crash land on an unknown planet similar to the Garden of Eden. Zapp shows his concerns for Leela's safety, causing Leela to gradually grow attracted to him. The two witness Earth's apparent destruction and decide to repopulate the human race à la Adam and Eve. At this point, however, Leela notices that some "fruit" Zapp had given her was actually trail mix Fry gave her, and Zapp confesses that everything was merely an elaborate scheme, including the Earth's destruction which was faked using a holographic projector from their ship, for her to think better of him and have sex with him. Furthermore, the two are actually on an island serving as the last unspoiled spot of nature on Earth. The V-GINY arrives at Earth and decides to spare it if "Adam" (Zapp) and "Eve" (Leela) have sexual intercourse, which they do much to the horror of the Planet Express crew.

Everyone in New New York buys the latest, state of the art eyePhone, a device developed by Mom which is implanted in a person's eye that allows users to record videos and post them online. Fry and Bender challenge each other to see who can gain one million followers on their Twitcher accounts, with the loser having to dive into a pool of goat vomit and diarrhea. With Bender in the lead, Fry resorts to posting an embarrassing video of Leela revealing she has a singing boil on her rear named Susan, gaining him enough followers to end the bet with a tie. However, Leela is humiliated, so Fry posts a video of himself diving into the pool out of guilt, which everyone watches and causes them to forget about the video of Leela. Fry and Leela reconcile, completely unaware that Mom has infected all of Fry and Bender's followers with a virus that turns them into mindless zombies to make them buy more eyePhones.

Kif breaks up with Amy when she begins showing interest in "bad boys", which leads her to become attracted to Bender. The two engage in a secret robosexual relationship, a taboo romantic relationship between a robot and a human, much to the prejudice of Farnsworth since one of his girlfriends from his youth left him for a robot. With the support of the rest of the crew, Bender and Amy become engaged and hold a ballot proposition called Proposition Infinity, which they hope will lift the ban on robosexual marriage, with Farnsworth representing the opposing party. While arguing against Bender, Farnsworth suddenly remembers that his old girlfriend was also a robot. Not wanting to lose the debate after revealing he too was robosexual, Farnsworth has a change of heart and supports Proposition Infinity, which is passed as law and legalizes robosexual marriage. However, Bender leaves Amy and begins dating fembots again when he realizes that robosexual marriage is monogamous. Fortunately for Amy, she gets back together with Kif after discovering that he has by now adopted a "bad boy" attitude for her.

Lrrr becomes unmotivated in his conquering of planets due to a midlife crisis. He tries to take over Earth to appease Ndnd, but fails when he arrives at Comic Con where he is mistaken for a costume contest participant, and is subsequently kicked out of his home by Ndnd. He moves into the Planet Express building and decides to take up dating again, falling in love with a female Omnicronian named Grrl until he discovers her to be a human in a costume who saw him at Comic Con. Lrrr decides to follow Leela's advice to win back Ndnd by staging an invasion of Earth broadcast by Orson Welles à la the 1938 "War of the Worlds" broadcast, which not only fools Ndnd, but also tricks Earth into actually surrendering. Leela scolds Lrrr and demands he tell Ndnd the truth, but he is unable due to her renewed romantic interest in him. Lrrr is later caught with Leela by the suspicious Ndnd and admits he faked the invasion and had an affair with Grrl, but Ndnd disregards those facts as she is only upset that he is letting Leela nag him. Lrrr is forced to prove his love to Ndnd by shooting Leela with a disintegration ray, but as he fires, Fry takes the shot and sacrifices himself to protect Leela. Ndnd gets back together with Lrrr since he was at least willing to shoot Leela, and Fry is found to be alive since the "disintegration ray" turns out to be a novelty teleportation ray.

After making their 100th delivery, for which Bender organizes a huge party, the Planet Express crew is invited to a fund raiser for giving sewer mutants the needed donations to keep them away from the surface. Seeing how upset Leela is by this, Fry publicly lets slip that she is a mutant living illegally on the surface, causing her to be banished to the sewers for life. Feeling guilty for ruining Leela's life, Fry and the Planet Express crew appeal to the mayor to let her live on the surface again, but they are instead banished to the sewers for two weeks for knowingly harboring a mutant on the surface, minus Bender, who is enjoying the party. To appease Leela's anger and understand the life of a mutant, Fry jumps into a pool of toxic waste and emerges as a hideous blob. Leela is moved by Fry's sacrifice and decides to lead a mutant rebellion against the surface people by getting Bender, who ends up stopping the party after realizing it is no fun without the rest of the crew, to bend the giant sewer pipes together, thus backing up all the pipes around the city and flooding the surface with sewage. The mayor complies to the mutants' demands for equal rights, allowing them to finally live on the surface. Furthermore, it is revealed that Fry had not mutated, but was merely stuck in the body of another mutant. Afterwards, the Planet Express crew has a second "100th Delivery" party since they missed out on the first.

Guest star: Mark Mothersbaugh as himself

A holiday special featuring three holiday-themed segments, following the same structure as the episodes "Anthology of Interest I" and "Anthology of Interest II." The three segments are based around the three winter holidays previously featured on Futurama: Xmas, Kwanzaa and Robanukah.

Bender creates duplicates of himself to get out of doing work, but the clones end up replicating and causing mass intoxication when they reach atomic level and manipulate the water molecules into alcohol. Meanwhile, an ugly space giant (voiced by Patton Oswalt) invades Earth.

Bender commits suicide (actually gets murdered, since the suicide booth is still bitter over Bender dumping her) after Fry saves a human during the Parade Day parade instead of a robot, and the only way out of being a wandering spirit is to scare Fry to death by haunting him.

After failing at telling a story to the children at her old orphanarium, Leela comes up with a new story about weird aliens who laugh, sing, and learn important life lessons, which makes her the creator of the Tickelodeon Network's newest show -- until Bender learns the secret behind Leela's success.

Fry inadvertently reintroduces the common cold (which died out 500 years before Fry was revived) to the 31st century, while flashbacks tell the story of how Fry adopted a guinea pig for a school science project.

An episode featuring Futurama animated in three retro styles: "Child Labor Syndicate Presents: Colorama in Glorious Black and White" has Futurama as a black-and-white, rubber-hose cartoon from the 1930s, "Future Challenge 3000" has the show as an early 1980s low-resolution video game, and Action Delivery Force has the show as a 1970s Japanese cartoon.