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|“||This is getting old, Jack!||„|
|~ Ethan to a monster formed Jack during their final battle.|
|“||Do me a favor and stay dead.||„|
|~ Ethan after he defeated Jack in second boss.|
|“||Just fucking stay dead – OK?||„|
|~ Jack after killed Marguerite.|
|“||What the hell is she? Now what did she do to you?||„|
|~ Ethan to the real Jack about Eveline's infected the Bakers|
Very little is known about Ethan's past prior to the events of the game other than that he met and married Mia Winters before 2014. Mia had sent him a video of her telling him about her babysitting job, which was the last video message he received from her.
In July 2017, Ethan received an e-mail from a woman claiming to be his wife who was reported deceased in 2014. Ethan journeyed out to Dulvey, Louisiana in search of her, taking him to the "Dulvey Haunted House" formerly owned by the Baker family until their own disappearance that same year. He enters the house and watches the "Derelict House Footage" (as seen in the Beginning Hour demo), where he witnesses the Sewer Gators team - cameraman Clancy Javis, producer Andre Stickland and anchorman Pete Walken - infiltrate the house, ending with Clancy discovering Andre's dead body. He travels through an underground shaft, and after discovering Andre's decaying corpse floating in the water, he finally finds Mia. After freeing her, she claims to not know about any message given to him and guides him to escape from the house's occupants. He receives phone calls from a woman named Zoe, who tells him to go to the attic. However, Mia, clearly possessed by infection, attacks him with a knife and later a chainsaw, hacking off Ethan's left hand and forcing him to shoot her dead. As Ethan attempts to escape, Jack Baker appears and knocks him out.
With his left hand stapled (presumably by Zoe) and a codex showing him his health, Ethan awakens in a dining room where he meets the Baker family - Jack, his wife Marguerite, son Lucas, and an unnamed, silent elderly woman - who are eating human parts. He is force-fed their food until a policeman forces them to hide. He manages to escape his bonds but Jack is still around and starts looking for him. As Ethan tries to find a place to hide, Jack catches him and dismembers the lower half of his leg. He then provides Ethan a strong first aid med that allows him to reattach his leg. Once Ethan gets away for Jack through a passageway under the floor, he later meets a police officer at a window, who gives him his knife. The two meet in the garage, where the officer is killed by Jack, who fights Ethan until the latter wears him down and kills him.
Zoe reveals over the phone that the Bakers and Mia have been contaminated by a mysterious pathogen, requesting that Ethan set out to retrieve the necessary items to develop a serum which can cure her and Mia so that they can escape the Baker residence.
Ethan sets out to find the necessary items to leave the main house, only to face off against the resurrected Jack, who reveals himself to be seemingly immortal. The two engage in combat in the basement of the house before Ethan seemingly manages to finish Jack off once and for all in a chainsaw duel.
Traveling to the guest house, Ethan struggles to escape Marguerite and the bug swarms she controls, eventually being trapped and forced to defeat her head on. The confrontation leads to his discovery of the mummified corpse of a "D-Series" child, the basis of the serum needed by Zoe.
- He's a civilian throughout his entire life and does not have the professional fighting skills that most of the previous Resident Evil protagonists displayed.