In the United States, the series aired on Fox from March 28, 1999, to August 10, 2003, and aired in reruns on Cartoon Network's Adult Swim from 2003 to 2007. It was revived in 2007 as four direct-to-video films, the last of which was released in early 2009. Comedy Central entered into an agreement with 20th Century Fox Television to syndicate the existing episodes and air the films as 16 new, half-hour episodes, constituting a fifth season.
Futurama is essentially a workplace sitcom, the plot of which revolves around the Planet Express interplanetary delivery company and its employees, a small group that largely fails to conform to future society. Episodes usually feature the central trio of Fry, Leela, and Bender, though occasional storylines center on the other main characters.
- Philip J. Fry (Billy West) – Fry is an immature, slovenly, yet good-hearted and sentimental pizza delivery boy who falls into a cryogenic pod, causing it to activate and freeze him just after midnight on January 1, 2000. He reawakens on New Year's Eve of 2999, and gets a job as a cargo delivery boy at Planet Express, a company owned by his only living relative, Professor Hubert J. Farnsworth. Fry's love for Leela is a recurring theme throughout the series.
- Turanga Leela (Katey Sagal) – Leela is the competent, one-eyed captain of the Planet Express Ship. Abandoned as a baby, she grows up in the Cookieville Minimum Security Orphanarium believing herself to be an alien from another planet, but learns that she is actually a mutant from the sewers in the episode "Leela's Homeworld". Prior to becoming the ship's captain, Leela works as a career assignment officer at the cryogenics lab where she first meets Fry. She is Fry's primary love interest and eventually becomes his wife. Her name is a reference to the Turangalîla-Symphonie by Olivier Messiaen.
- Bender Bending Rodriguez (John DiMaggio) – Bender is a foul-mouthed, heavy-drinking, cigar-smoking, kleptomaniacal, misanthropic, egocentric, ill-tempered robotmanufactured by Mom's Friendly Robot Company. He is originally programmed to bend girders for suicide booths, and is later designated as assistant sales manager and cook, despite lacking a sense of taste. He is Fry's best friend and roommate. He must drink heavily to power his fuel cells and becomes the robot equivalent of drunk when low on alcohol.
- Professor Hubert J. Farnsworth (Billy West) – Professor Farnsworth, also known simply as "the Professor", is Fry's distant nephew. Farnsworth founds Planet Express Inc. to fund his work as a mad scientist. Although he is depicted as a brilliant scientist and inventor, at more than one-hundred and sixty years old he is extremely prone to age-related forgetfulness and fits of temper. In the episode "A Clone of My Own", the Professor clones himself to produce a successor, Cubert Farnsworth (Voiced by Kath Soucie), whom he treats like a son.
- Amy Wong (Lauren Tom) – Amy is an incredibly rich, blunt, spoiled, ditzy, and accident-prone long-term intern at Planet Express. She is an astrophysics student at Mars University and heiress to the western hemisphere of Mars. Born on Mars, she is ethnically Chinese and is prone to cursing in Cantonese and using 31st-century slang. Her parents are the wealthy ranchers Leo and Inez Wong. She is promiscuous in the beginning of the series, but eventually enters a monogamous relationship with Kif Kroker. In the show's sixth season, she acquires her doctorate.
- Hermes Conrad (Phil LaMarr) – Hermes is the Jamaican accountant of Planet Express. A 36th-level bureaucrat (demoted to level 37 during the series) and proud of it, he is a stickler for regulation and enamored of the tedium of paperwork and bureaucracy. Hermes is also a former champion in Olympic Limbo, a sport derived from the popular party activity. He gave up limbo after the 2980 Olympics when a young fan, imitating him, broke his back and died. Hermes has a wife, LaBarbara, and a 12-year-old son, Dwight.
- Dr. John A. Zoidberg (Billy West) – Zoidberg is a Decapodian, a lobster-like alien from the planet Decapod 10, and the neurotic staff physician of Planet Express. Although he claims to be an expert on humans, his knowledge of human anatomy and physiology is woefully inaccurate. Zoidberg's expertise seems to be with extra-terrestrial creatures. Homeless and penniless, he lives in the dumpster behind Planet Express. Although Zoidberg is depicted as being Professor Farnsworth's long-time friend, he is held in contempt by everyone on the crew.
- Zapp Brannigan (Billy West) – Zapp Brannigan is the incompetent, extraordinarily vain captain of the DOOP starship Nimbus. Although Leela thoroughly detests him, Brannigan—a self-deluded ladies' man—pursues her relentlessly, often at great personal risk. He was originally going to be voiced by Phil Hartman, but Hartman died before production could begin.
- Kif Kroker (Maurice LaMarche) – Zapp Brannigan's 4th Lieutenant and long-suffering personal assistant, Kif is a member of the amphibious species that inhabits the planet Amphibios 9. Although extremely timid, he eventually works up the courage to date Amy. Kif is often shown sighing in disgust at the nonsensical rantings of his commanding officer.
- Mom (Tress MacNeille) – Mom is the malevolent, foul-mouthed, cruel, and narcissistic owner of MomCorp, the thirty-first century's largest shipping and manufacturing company, with a monopoly on robots. In public, she maintains the image of a sweet, kindly old woman by speaking in stereotypically antiquated statements and wearing a mechanical fat suit. She occasionally launches insidious plans for world domination and corporate takeover. She has a romantic history with the Professor which left her bitter and resentful. She has three bumbling sons, Walt, Larry, and Igner (modeled after The Three Stooges), who do her bidding despite frequent abuse, and often infuriate her with their incompetence. In Bender's Game, it is revealed that Igner's father is Professor Farnsworth.
- Nibbler (Frank Welker) – Nibbler is Leela's pet Nibblonian, whom she rescues from an imploding planet and adopts in the episode "Love's Labours Lost in Space". Despite his deceptively cute exterior, Nibbler is actually a highly intelligent super-being whose race is responsible for maintaining order in the universe. He is revealed in "The Why of Fry" to have been directly responsible for Fry's cryogenic freezing. While the size of an average house cat, his race is capable of devouring much larger animals. He defecates dark matter, which until Bender's Game is used as fuel for space cruisers in the series.