After a devastating spaceship crash, Professor Farnsworth attempts to resuscitate the crew with his birth machine. Following the events of Futurama: Into the Wild Green Yonder, all the characters will be reborn. The episode will focus on the relationship between Fry and Leela.

In 1998, two artificial satellites were launched into Earth's orbit. Shortly after launch, the two mysteriously disappeared. Sometime in the 31st century, a death sphere (a parody of death star) appears, destroying planets in its path. Zapp Brannigan and Turanga Leela are sent to destroy the death sphere in an undetectable one-manned ship built by Farnsworth.

An unflattering video of Leela makes the rounds online, thanks to Fry. The episode will feature what ends up of Facebook, iPod, iPhone and Twitter in the future. Mom is to control Twitter, while Bender hacks into Facebook. Fry and Leela get the citizens of Earth to use their eyePhones to decide who will win.

Amy and Bender fall in love and begin a culturally taboo "robosexual" relationship. After facing anti-robosexual sentiments from society, they elect to get married and advocate to legalize robosexual marriage through "Proposition Infinity."

The Planet Express crew races to future Rome to unearth the shocking secret of Leonardo da Vinci.

Bender learns that he suffers from a terminal manufacturing defect, effectively rendering him mortal. Bender must cope with his new found mortality and employs Hermes Conrad's help to track down the mysterious quality inspector-Inspector #5-whom he blames for allowing him to enter the world only to die.

The Professor invents a one-way time machine. He and Fry go forward 1,000 years accidentally, and keep traveling forward in time until a backwards time machine has been invented.

Amy's rejected doctoral dissertation—a device to harness the Earth's rotational energy—is used by evil invading space cats to fix their own slowing planet. Since the invention will cause the Earth to stop turning, Amy and Nibbler must team up to stop them while their co-workers have fallen under the thrall of the cats' cuteness.

Professor Farnsworth leaves Earth after being frustrated by anti-evolutionists' illogical belief in "Creaturism", a form of Creationism. He and the Planet Express crew arrive at a lifeless planet and the Professor introduces nanobots into the environment. The nanobots rapidly begin evolving into mechanical organisms, allowing the crew to witness a whole new evolutionary history that unfolds before their eyes.

Professor Farnsworth and Amy build a machine that allows them to switch minds so that they may each pursue their lifelong dreams. However, they learn that the machine cannot be used twice on the same pairing of bodies. To try to return to their rightful bodies, they involve the rest of the crew in the mind switches, leaving each member free to pursue their own personal endeavors in a different crew member's body.

The ruler of the planet Omicron Persei 8, Lrrr experiences marriage trouble with his queen, Ndnd. He departs for Earth, invading it in an attempt to overcome his mid-life crisis and reignite his marriage.

The Planet Express crew is hired for their 100th delivery. To celebrate, Bender organizes the biggest party of the millennium. During a fundraiser, Fry inadvertently exposes Leela as a mutant illegally living on the surface. Leela is subsequently banished to the sewers to live in squalor with the other mutants. The crew, with the assistance of the mutated members of Devo, follow Leela in an uprising against the surface dwellers.

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

An alien who does not understand the concept of gender conducts experiments on the crew, changing all their genders.

Bender creates duplicates of himself, who in turn create duplicates of themselves, until they threaten to consume all of the matter on Earth.

Bender, angry at Fry for valuing human life over robot life, kills himself in a suicide booth. Afterwards, he becomes a ghost, and learns from the Robot Devil that he is in limbo, and he cannot leave. Sharing a mutual dislike towards Fry, the Robot Devil offers to return Bender to his old body in exchange for using his new ghostly powers to scare Fry to death.

Fed up with his go-nowhere job, Fry joins the police force.

Bender goes into witness relocation after testifying against the robot mafia.

Leela creates a successful new series, and becomes a Hollywood bigshot.

Professer Farnsworth licks George Washington's head and it sends him on a trip to the Revolutionary War.

Professor Farnsworth sends the Planet Express to find a statue of his crew for the 50th memorial service honoring their disappearance.

Fry nurtures an alien egg that hatches into a horrific monster.

The crew learns shocking secrets of how Professor Farnsworth and Dr. Zoidberg met.

Fry inadvertently reintroduces the common cold to the 31st century.

Bender is overclocked, gradually becoming more powerful in computing ability, until eventually becoming omniscient and able to foresee events in the future.

Futurama is seen in three different animation styles. Each segment showcases a different style of animation. The first segment is animated in "a black-and-white Fleischer style", the second segment drawn in the style of anime, and the third is in the style of a low-resolution video game. The plot of each segment form part of an overall story arc, revolving around the discovery and subsequent destruction of a Diamondium comet.