The least capable delivery crew, and the only one at Planet Express, are back once again. Fry, Leela, and Bender the robot continue to carry out all sorts of jobs across the known universe, while trying to make a living on Earth alongside their boss, Professor Hubert Farnsworth, and the rest of the staff. Their new adventures will lead them to discover mysterious curses, encounter more time travellers like Fry, end up on a planet of Amazonian warriors, take on a film shoot, and cause a rift in time that threatens the very existence of the universe.

The second series of Futurama covers various adventures of the Planet Express crew, including Fry and Bender enlisting in the army for a war against spherical aliens, Bender turning into a were-car after being struck by one, and the crew being forced to reenact the final episode of a sitcom to save Earth from an alien invasion.