This Resident Evil 2 is a remake of the original game with the same title that came out 20 years and four console generations earlier. In terms of story and gameplay, the game tries to stay true to the original. Even reading collected notes and handling inventory items feels purposely outdated with less real-time feel to capture the original feel. The graphics are pretty much the main boost that separates this game from the original, and it runs on RE Engine introduced in Resident Evil 7.

The story follows Leon S. Kennedy, a rookie police officer coming to work on his first day at Raccoon precinct. Alternate story follows Claire Redfield, who came to Raccoon city in search of her brother, Chris, who is also a S.T.A.R.S. team member. The game, just like the original, is intended to be played with both characters, where second playthrough with different character will unlock additional locations and complete the story. Thus the story works the same if played first as Leon and then Claire, or first as Claire and then Leon. The stories aren't entirely in parallel and replaying with a different character, while opens new locations, cutscenes and boss battles, will also force player to unlock the same lockers, doors and paths that the other player did on the first playthrough. During the main story, Sherry, in Claire's story, and Ada Wong, in Leon's story, are playable for a bit.

By completing the game, new gameplay modes get unlocked which feature other characters such as Hunk or Tofu Survivor. While the original game used fixed scenes with pre-rendered background and tank controls for the characters, this remake uses real-time 3D graphics with shoulder camera and directional controls. Many locations and cut-scenes are recreated to match the original, though there are also entirely new areas included in this remake that the original game didn't feature. Similar to original RE2, various artwork can be unlocked by collecting it throughout the game. Unlocked artwork and 3D models can be accessed via main menu.

Unlike the original game, this release has various DLCs which add new outfits and weapons to use in the game. Some of the bonus outfits, such as the original 1998 outfits with new graphics, however, become available upon completing the main story. Similar to Chris Redfield's new character facial seen in RE7, both Leon and Claire deviate from their standard looks due to Capcom using motion-capture for character facials so they looked for an actor with close resemblance to the original character not to go way off the familiar appearance.