In 2014, BSAA agent
Chris Redfield is tracking Glenn Arias, a former
CIA operative-turned arms dealer. Arias, wanting revenge against the U.S. government for killing his friends and family in a
drone strike at his wedding, is developing and smuggling bioweapons into the country, so Chris and other agents infiltrate a mansion in
Mexico, to rescue their missing undercover source, Cathy White. There, Chris's fellow agents are ambushed by zombies and death traps, with Chris being the sole survivor. Outside the mansion, Chris faces Arias, who reveals that Cathy has become a zombie under his control. As Arias leaves with his associates, father and daughter Diego and Maria Gomez, the BSAA rescues Chris by slaughtering Cathy and the remaining zombie horde. Four months later, Professor
Rebecca Chambers, former S.T.A.R.S. unit member and survivor of the
Mansion Incident, studies the new "Animality Virus"—"A-virus" for short—that can lay dormant inside any individual until the right trigger is presented. The virus has three components: the base virus, the triggering virus, and the vaccine. Maria attacks the research labs and releases the virus via the
aerosol form. While her colleagues turn into zombies, Rebecca formulates a vaccine to make herself immune and is eventually rescued by Chris and his BSAA team: D.C., Damian, and Nadia. He briefs her on his mission. Rebecca recognizes the zombies' loyalty to the host and makes a connection to Las Plagas, the
bioweapon used by the Los Illuminados who Division of Security Operations (DSO) agent
Leon S. Kennedy once encountered in Europe, theorizing that the remaining members of the cult are providing information to Arias in developing the A-virus. She, alongside Redfield, heads to
Colorado to bring Leon on board but is unwilling at first after experiencing guilt on having to kill the infected SWAT team sent to back him up during a viral outbreak disguised as a bomb threat and his repetitive experiences. During this conversation, Maria and Diego attack the trio. They successfully capture Rebecca, while Chris and Leon, who agree to help finish the mission, devise a rescue operation, decrypting Arias' plan of a large-scale viral attack on
New York City. Arias then challenges Chris to rescue Rebecca, who is injected with a vaccine-resistant virus that threatens to turn her into a zombie as part of his personal plan to re-start the failed wedding. As Arias' associates initiate their attack on New York by releasing the virus-laden gas via tankers, Leon and Chris' BSAA team destroy the vehicles and contain the virus, incapacitating Maria in the process, but Damian is killed by zombie dogs. Chris, later joined by Leon, then infiltrates Arias' safe house, defeats Diego, and rescues Rebecca. On the terrace, Chris engages Arias in combat and throws him through a glass terrace to his demise. Diego then arrives and, despite being badly injured after being defeated by Chris, merges with Arias to form a new Tyrant monster. Chris is no match against the Tyrant until Leon joins the fight after working through the safe house, mowing down zombies. With the assistance of D.C. and Nadia, they trap the Tyrant before Leon and Chris kill it. They locate the antidote that Arias kept and cure Rebecca before escaping by helicopter. The team then spreads the antidote across the city to cure the rest of the infected. Meanwhile, Maria, later revealed to be alive, discovers her now-dead father. ==Voice cast==