Resident Evil 6 is a survival horror game which continues the struggle against the series' signature bio-terror-inducing zombies. Players can select between three scenarios featuring multiple characters and intertwined storylines. Within these scenarios both stories and action cross paths.

Unlike in some previous Resident Evil games where different scenarios meant different characters going through the same storyline and locations, in Resident Evil 6 each scenario has its own scenes, locations, weapons, and unique enemy types. The main three scenarios are for Leon (the protagonist of Resident Evil 2 and 4), Chris (Resident Evil, Code Veronica and Resident Evil 5) and Jake (a new character in the series). Each of those scenarios is a two-player story, either in co-op or with a computer-controlled partner. After finishing all three scenarios, a bonus scenario becomes available, where it is possible to play through Ada Wong's story.

Additional features include new enemies, upgradable firepower and characters, vehicle based options, the mini-game based Mercenaries mode, and single-player and co-op play options.