Gary King (Simon Pegg), a middle-aged alcoholic, tracks down his estranged schoolfriends and persuades them to complete "the Golden Mile", a pub crawl encompassing the 12 pubs of their hometown of Newton Haven. The group had previously attempted the crawl as teenagers in 1990 but failed to reach the final pub, The World's End.
Gary arrives in Newton Haven with friends Peter (Eddie Marsan), Oliver (Martin Freeman), Steven (Paddy Considine), and Andy (Nick Frost), and they begin the crawl. In the second pub, the group is briefly joined for a drink by Oliver's sister Sam (Rosamund Pike), whose affections Gary and Steven fought over in school. At the third pub, Gary is turned away due to being barred as a teenager, but drinks some beer left behind on a table outside. In the toilets of the fourth pub, Gary picks a fight with a teenager and knocks his head off, exposing a blue blood-like liquid and subsequently exposing him as an alien android. Gary's friends join him and fight more androids, whom they refer to as "blanks" to disguise what they are talking about.
They decide to continue the pub crawl so as not to make the androids suspicious of their actions, as Gary had told various people that they were doing the Golden Mile. At the seventh pub, the group runs into Sam again. In the garden, Gary, Sam and Steven get into a fight with androids impersonating Sam's twin friends, making Sam convinced of the androids' invasion after previously not believing Gary. At the eighth pub, androids impersonating attractive girls from their youth attempt to seduce Gary, Andy and Peter, while Basil, a man whom they had spoken to in their previous pub crawl in 1990 and who had been known for making wild theories, explains to Steven the details of the android invasion. At the ninth pub, Guy Shepherd (Pierce Brosnan), their old schoolteacher, encourages them to accept their fate and be replaced by androids. Andy realises that Oliver has been replaced with an android after seeing the return of his birthmark, which he had earlier told he had removed with cosmetic laser treatment, and crushes his head with a barstool. Another fight breaks out and the group scatters. Gary and Sam escape the pub together and Gary tells her to leave for her own safety.
Once reunited, the four remaining friends accuse each other of having been replaced by androids, but prove that they are human. At this point, it is revealed that earlier in their adult life, Gary had betrayed Andy and allowed him to be arrested and almost killed, explaining Andy's hostility towards Gary. The androids close in on the group and capture Peter after he picks a fight with the android representing his former childhood enemy, but Gary is determined to finish the pub crawl. However, Andy refuses and demands that they return to London, knocking Gary out in the process to make him go with them. Andy and Steven find that to get to the car, they must go through the tenth pub, where Gary wakes up. After having his tenth pint, he decides to carry on alone, which leads to Andy chasing after him. After quickly having a drink at the eleventh pub, he runs towards the final pub, the World's End. Steven is overwhelmed by the androids while attempting to drive the car away, and Andy continues to chase Gary towards the final pub.
At the World's End, Andy confronts Gary. In the quarrel, Andy reveals that his wife has left him, and realises that Gary attempted suicide in the years since school. As he tries to stop Gary from drawing his final pint, they discover a hidden chamber and are reunited with Steven. A disembodied alien entity, the Network (Bill Nighy), reveals that the limited android invasion has been responsible for all of humanity's advances in telecommunications in recent decades, bringing humanity closer together as a first step to joining the galaxy's community of planets. The Network offers the men the chance to contribute to Earth joining the galactic community, even offering them eternal youth by becoming androids, but they refuse as they point out the numerous flaws in The Network's plan. Exasperated, the Network abandons the invasion after Gary manages to prove that the Network had to replace nearly all of the citizens in the town to make it acceptable enough for its standards. Sam arrives just in time to drive the group out of Newton Haven as it self-destructs.
Some time later, Andy recounts this story around a campfire in the ruins of London. The destruction of Newton Haven triggered a worldwide chain reaction that wiped out modern technology and sent humanity back to the Dark Ages. The remaining androids have reactivated and are mistrusted by surviving humans. Andy's marriage has recovered, Steven is in a relationship with Sam, android Peter returned to his family, and android Oliver returned to his estate agent's job (with a new head made out of a football). In the ruins of Newton Haven, the now-sober Gary enters a pub with the younger android versions of his friends and orders five glasses of water. When the bartender refuses to serve androids, Gary draws a sword and leads his android friends into a brawl.