Serien kretsar kring Philip J. Fry, pizzabud i New York som blir nedfrusen vid midnatt den 31 december 1999 och tinas upp tusen år senare, år 2999, precis i tid för nästa millennieskifte. Hans enda levande släkting är den nästan 160 år gamla professor Farnsworth, som äger budfirman "Planet Express", där Fry får jobb som bud. Tillsammans med de andra på firman råkar han ut för allehanda underliga äventyr.
Billy West
Fry / Professor Farnsworth / Zoidberg / Zapp Brannigan
John DiMaggio
Bender
Katey Sagal
Leela
Phil LaMarr
Hermes Conrad
Lauren Tom
Amy Wong
Professor Farnsworth invents a button that can take a person 10 seconds back in time, inadvertently causing major consequences.
In the fifth season, Bender grows jealous when Fry attempts to clone his beloved fossilized dog; when Kif gets pregnant, Amy questions her readiness to become a parent; when Fry and Leela discover a mysterious cream that gives them unusual powers, they form a Superhero team along with Bender; and Fry makes a deal with the Robot Devil so he can become a skillful musician and win Leela's heart.