Umbrella Security Service (USS) Delta team enters the Raccoon City Underground Laboratory, where they meet up with Alpha team leader HUNK. Their mission is to assist Alpha team in stopping Dr. William Birkin from handing over his T-virus research to the U.S. military and retrieve the G-virus. On their way to Birkin's lab, they find Birkin has paid numerous Umbrella Biohazard Countermeasure Service (UBCS) mercenaries to work for him while the deal goes forward. When they reach Birkin's lab, the doctor is shot, and HUNK and another Alpha leave with the samples. They soon find that Birkin survived the attack and infected himself with the virus. The Birkin creature proceeds to kill off most of Alpha team before disappearing; HUNK offers to go back in search of the sample.
There are 12 playable characters in the game, with six characters for each side. On the Umbrella Security Service team there is: Vector (Andrew Kishino), the team's recon expert and is equipped with a cloaking ability; Beltway (Ramon Fernandez), who is proficient in the use of explosives; Bertha (Lydia Look), the medic; Spectre (David Cooley), the marksman; Four Eyes (Gwendoline Yeo), the scientist, with the ability to program the bio-organic weapons (BOWs); and Lupo (Nika Futterman), who is the team leader. On the United States Special Ops team, Willow (Rebecca Riedy) is the recon expert; Dee-Ay (Robin Atkin Downes) is the team leader; Tweed (Tess Masters) is the demolitions expert; Harley (Gregg Berger) is the medic; Shona (Imari Williams) is the field scientist; and Party Girl (Catherine Taber) is the sniper.
The zombies in the game are able to attack the player in a multitude of ways. A zombie that gets too close to the player will usually attempt to grapple the player, prompting the player to rapidly shake his/her analogue stick to avoid getting bitten. Players who are unsuccessful in doing this will be infected for a limited amount of time. Whilst they are infected they gain small bonuses at the expense of a slowly depleting health bar. If a player is successfully bitten and later runs out of time after becoming infected, the player will lose control of their character and begin attacking their former teammates until killed, allowing the player to respawn. There are additional enemy types in the game besides zombies, such as Lickers, Hunters, and Cerberuses. Furthermore, the players are able to control them under certain circumstances.