Resident Evil: Outbreak begins a couple of days after the initial outbreak in Raccoon City, moments before the crisis erupts into complete chaos. The game ends in the final moments of the incident, with the player attempting to escape Raccoon City before the U.S. government launches a missile strike to eliminate the threat posed by the T-Virus. The player controls one of eight characters, or numerous supporting characters who can be selected in their place. Events transpire across various regions of Raccoon City and over a period of several days. Events also span from Resident Evil 2-3.

Resident Evil: Outbreak was originally known as Resident Evil: Online. Capcom released various pieces of media under this name in 2002, including pictures featuring the eight main characters wandering around the Arklay Mountains and a trailer demonstrating the ad-lib system and character communication.

The title was later changed to Resident Evil: Network and information was given that the game included over twenty scenarios. The title was changed again to Resident Evil: Outbreak with reduction in the number of scenarios to five.

Resident Evil: Outbreak presents the first time in the series that players have been given multiple melee weapons, and even their own bodies (via kicks, shoves and rams), to use against enemies. However, many such weapons are very weak and still no match for a firearm of some kind, and should only be considered a last resort. Weapons and physical strikes can also be used to break down doors instead of opening them manually, although some enemies have the capacity to do the same.

If you attempt play Outbreak like you would have the previous games you will receive a very painful lesson. You cannot go room to room anymore to clear out a level. In most areas killing a zombie just gives the game a cue to have another zombie bash its way through the door to replace that one. Some areas are "safe" but the general rule is to kill only when you cannot run away in order to save ammunition for tougher enemies and bosses.