Afterlife begins by going back in time to the zombie outbreak when it first hits Tokyo. Going into the present, the Alice clones invade the Umbrella Tokyo Headquarters and eventually make it to Wesker. However, Wesker manages to escape in a plane and blows up the facility, presumably killing all of the Alice clones, thus ending that particular plot point. However, the real Alice is onboard Wesker's plane and attempts to attack him, but Wesker injects Alice with some kind of anti-virus that neutralizes her powers. Wesker nearly kills Alice, but the plane crashes into Mt. Fuji, allowing Alice to escape from Wesker.

Alice resumes her search for the survivors from Extinction that left on the chopper for Alaska. She makes it to Alaska, but she finds the chopper empty. Suddenly, Claire Redfield, being possessed by the same chest machine used on Jill in RE5, attacks Alice, but Alice is able to remove it. Claire is suffering from memory loss and doesn't remember Alice. Claire cooperates with Alice anyway, and they both fly down to Los Angeles to search for more survivors.

They land their plane on a prison where a few survivors are being kept. The survivors believe that Alice and Claire were from Arcadia, who had been broadcasting the signals of safety and security since the previous film. Arcadia is actually a ship in a harbor near LA, seemingly uninfected. However, Arcadia stopped broadcasting a few days earlier. The survivors want to make it onto the ship, so they plot an escape. Chris Redfield has been imprisoned this whole time by the survivors because they thought he was an ex-prisoner, but Chris knows a good escape route, so the survivors trust him. Chris recognizes Claire, but she is unable to after suffering from her memory loss. However, the Executioner and the Majini Zombies invade the prison, causing all but two of the survivors to die. After finishing the Executioner off, Alice, Claire and Chris eventually make it onto Arcadia, which turns out to have been a ploy by Umbrella to trick humans into seeking shelter in Arcadia only to become experiments.

Wesker happens to be on the ship, having tracked Alice down because he needed her flesh to keep his T-Virus infection in check. A huge battle ensues, modeled after Chris and Sheva's various battles with Wesker. Chris and Claire attempt to take Wesker down, but they're unsuccessful at first. Alice steps in and is finally able to neutralize Wesker before Chris and Claire finally finish him off. As they take care of the survivors and former Umbrella experiments, Wesker resurrects himself and attempts to leave the ship on a plane, triggering a bomb that would blow up the ship. However, Alice has already snuck the bomb onto Wesker's escape plane, blowing up the plane and killing him for good.

Alice, Chris and Claire assume command of Arcadia and turn it into a real safe haven from the zombie apocalypse. The ending is quite a huge surprise, as a bunch of Umbrella fighter planes are headed towards Arcadia. One of them is under the command of Jill Valentine, in her RE5 battle suit, under control by the same red machine that controlled her in RE5 (and Claire earlier in the movie). Jill Valentine tells her troops that their main targets are Chris and Claire Redfield, and Project Alice, leading into what will presumably be part of the main plot of the next film.

it seems wesker death will be lame as hes screen time and they did go with that ending who the hell will be controlling jill if the boss is dead?

I find it so hilarious that they introduced the alice clones in extinction as some major plot point then in Afterlife they kill them all off in the intro, basically after they realized how STUPID of a plot point it is. Not that I'm complaining about the fact they all die, I'm all for that. I just find it hilarious they realized how STUPID their plot was and retcon'd it ASAP in the movie, thus making it even STUPIDER than it already was by simply erasing the plotline once they realized they had no where to go with a thousand alice's. Just shows how terrible of a writer Anderson is.

Also, Wesker needs Alice's flesh to survive? Lololololol oh god Anderson, you're too much

Also, Wesker needs Alice's flesh to survive? Lololololol oh god Anderson, you're too much