The story of Resident Evil follows the rise and fall of the Umbrella Corporation and the worldwide spread of deadly viruses, parasites, and bio-organic weapons (B.O.W.s). After the destruction of Raccoon City, the fight against bioterrorism expands across the globe as new organizations, viruses, and enemies emerge.

Resident Evil 2 takes place during the Raccoon City outbreak in September 1998. Rookie police officer Leon S. Kennedy arrives for his first day on duty, while Claire Redfield enters the city searching for her missing brother Chris. Together they survive the zombie-infested streets, uncover Umbrella's underground laboratories, and confront scientist William Birkin, who mutates after injecting himself with the G-Virus. They rescue Sherry Birkin and escape before the U.S. government destroys Raccoon City to contain the infection.

Resident Evil 3 occurs simultaneously with the events of Re2. Former S.T.A.R.S. officer Jill Valentine attempts to flee the collapsing city while being relentlessly hunted by Nemesis, a Tyrant created by Umbrella to eliminate surviving S.T.A.R.S. members. With the help of mercenary Carlos Oliveira, Jill survives infection by the T-Virus, defeats Nemesis, and escapes shortly before Raccoon City is obliterated by a nuclear strike.

Resident Evil 4 is set six years later. Leon S. Kennedy, now a U.S. government agent, is sent to rural Spain to rescue the President's daughter, Ashley Graham. He discovers that a religious cult known as Los Illuminados controls villagers through a parasite called Las Plagas. Leon battles cult leader Osmund Saddler, encounters the mysterious Ada Wong, rescues Ashley, and prevents the parasite from being used as a global bioweapon.

Resident Evil 5 follows BSAA agents Chris Redfield and Sheva Alomar in Africa as they investigate another bioterrorist incident involving Las Plagas and the Uroboros Virus. Their mission reveals that Albert Wesker plans to infect humanity and create a new world ruled by enhanced survivors. Chris and Sheva pursue Wesker to an active volcano, where they destroy him and stop the release of Uroboros, ending Umbrella's greatest remaining threat.

Resident Evil 6 depicts a worldwide bioterrorism crisis involving the C-Virus. Four interconnected campaigns follow Leon S. Kennedy, Chris Redfield, Jake Muller, and Ada Wong as attacks devastate the United States, Eastern Europe, and China. Leon is forced to kill the infected U.S. President, Chris overcomes the loss of his squad while hunting bioterrorist Carla Radames, Jake—Wesker's son—becomes the key to a possible cure, and Ada exposes Carla's conspiracy. Together they prevent a global catastrophe and destroy the Neo-Umbrella organization.

Resident Evil 7: Biohazard introduces Ethan Winters, an ordinary civilian searching for his missing wife Mia in rural Louisiana. Ethan discovers the Baker family, whose minds have been corrupted by Eveline, a bio-engineered weapon created using a mutamycete fungus. After surviving horrific encounters inside the Baker estate, Ethan defeats Eveline with assistance from Chris Redfield and the Blue Umbrella organization, rescuing Mia and uncovering a new biological threat unrelated to the classic viruses.

Resident Evil Village continues Ethan's story several years later. Chris Redfield apparently murders Mia and takes Ethan's infant daughter Rosemary, leading Ethan to a remote European village ruled by four powerful lords under Mother Miranda. Ethan defeats Lady Dimitrescu, Donna Beneviento, Salvatore Moreau, and Karl Heisenberg before confronting Miranda, who seeks to resurrect her deceased daughter using Rosemary's unique powers. Ethan learns that he had actually died during the events of Resident Evil 7 and had been kept alive by the mutamycete. Sacrificing himself, he destroys the fungal megamycete and kills Mother Miranda, allowing Chris to rescue Rosemary and escape as the village is destroyed. Ethan's sacrifice ensures his daughter's survival and ends Miranda's century-long experiment.

Resident Evil Requiem In 2026, FBI analyst Grace Ashcroft investigates a series of mysterious deaths connected to the ruins of Raccoon City. The investigation becomes personal because her mother, journalist Alyssa Ashcroft, was murdered at the Wrenwood Hotel years earlier. Grace discovers evidence of secret experiments conducted by Umbrella and becomes involved in a search for a powerful biological weapon called Elpis. Meanwhile, Leon S. Kennedy investigates the same conspiracy and suffers from the effects of his past exposure to biological weapons.

Their investigations lead them to secret laboratories beneath Raccoon City, where they uncover the truth about Oswell E. Spencer, Umbrella's founder, and his experiments. Elpis turns out not to be a weapon of mass destruction, but a powerful antiviral capable of neutralizing biological viruses.
Grace uses Elpis to save Leon, while the main antagonist Victor Gideon mutates into a monster and is defeated. In the end, Grace and Leon survive, while the discovery of the secret Umbrella facility exposes new information about the Raccoon City disaster and the company's experiments.