After a month of inactivity following the events of Bender's Big Score, having resulted in the universe being ripped apart, people decide to go on with their lives. Amy and Kif get married, and Fry starts a new relationship with a girl named Colleen. However, it is not long before he realizes that Colleen has four additional boyfriends. Fry is unable to accept that she can't settle for one man and breaks up with her.
Professor Farnsworth mounts an expedition to investigate the anomaly, beating his archrival Wernstrom in a game of "Deathball" to win the right to do so. When Bender is sent to explore it, his touch causes the anomaly to emit a shockwave, which sends the entire crew flying aimlessly into space. Farnsworth and Wernstrom discover that only living beings can pass through the anomaly unaffected; electrical things such as robots are destroyed. Before they can initiate another expedition, Zapp Brannigan is commissioned to destroy whatever is on the other side.
Meanwhile, both Fry and Bender feel alone and unwanted. Fry, in his depression, sneaks aboard Zapp's ship just before it takes off so that he can find solace on the other side of the anomaly; Bender, on the other hand, is approached by the fabled League of Robots, a secret society of robots led by his hero Calculon, and quickly becomes a very prestigious member due to his perceived hatred of humans.
As Fry enters the anomaly, Zapp's plan of attack unsurprisingly goes awry, and Kif is accidentally killed in the process, much to Amy's grief back on Earth. While drifting through space on the other side, which contains another universe, Fry comes across a colossal, one-eyed, tentacled creature, which begins forcing its appendages through the anomaly. The tentacles begin attacking everyone on Earth, and there is absolutely no stopping them as they are made of electromatter, which can only be harmed by other electromatter. Fry returns to Earth, having been attached to one of the tentacles, and tells everyone to submit to them, as he has fallen in love with the creature they're attached to. Fry becomes the pope of a religion worshipping the tentacles. The tentacles begin attaching themselves to the back of everyone's necks, causing them to love the creature as well.