The remake features all-new graphics and sound, and also incorporates gameplay elements from the earlier installments (such as the use of body language and the 180 degree turn). While the overall plot remained mostly unchanged (with the exception of adding the George Trevor diaries and, in the case of the Barry Lives ending, the implication that Wesker managed to escape into the night), several new areas and rooms were added to the game, including a graveyard and a cabin in the woods. In addition, other areas are also condensed. A notable example is the room the Tyrant and Wesker were in. Originally, they were two separate rooms, with Wesker either forcing Chris/Jill by gunpoint to the former room or, in the case of one of the Barry Lives endings, Jill and Barry going in out of their own volition after Wesker was knocked out. In the REmake, the rooms were combined together. The original live-action FMV segments are replaced by CG versions, and the voice acting was completely re-recorded with new actors. Chris and Jill are still the only two selectable characters. However, if Chris gets poisoned by Yawn, you have to play as Rebecca Chambers to get serum for Chris; there are also some other occasions when you have to play as Rebecca. Most of the puzzles have been changed, and the player's character is now also equipped with a defensive weapon that can be used while being grabbed by the enemy. Both characters have access to dagger (can be retrieved from ground if player decapitates the attacked enemy). Jill's exclusive defense item is stun gun, a weapon that temporarily floors enemies in the ground if they were at full health(exception of chimeras and tyrant) and Chris' defense item is flash grenade, a weapon that can instantly decapitate most of the enemies. It is necessary in this game to decapitate or burn zombies using a lighter (Chris starts his scenario with one, while Jill has to find one in the mansion) and fuel canteen together to prevent them from regenerating later in the game as the fast and deadly "Crimson Head". Take note that you'll find fuel canteen empty and have to load it from gasoline tanks which has 4 uses (6 on easy and very easy plus fuel canteen can be loaded with max 2 liters at a time). The four crests from the original (sun, moon, wind, and star) used to unlock the door to the courtyard are still present, but instead are used to obtain the Colt Python (magnum) in the graveyard. Another change in the game was the environment: several picture display cases were seen shattered, implied to be either from Albert Wesker himself or Barry Burton under Wesker's influence in order to cover up Wesker's involvement in Umbrella. In the original game, the picture display cases were not shattered. Another change is players can perform critical headshots on zombies using handgun at any time. (Chris has better chance than Jill due to his better aim.) Shotgun and magnum can also no longer has a %100 decapitation rate on zombies. The only weapon that has %100 decapitation rate is Chris' flash grenade. The monsters' health also doesnt change depending to the character that was chosen.
The game also features many additional modes, secrets, and various endings over the original, as well as restoring the George Trevor sub-plot from the pre-release versions of the original game, while adding his daughter Lisa into the game as a transformed monster (and source of the G-virus). Other additions bring Umbrella researcher William Birkin and Alexia Ashford into the overall plot to make links between the games more clear and numerous.
For the HD Remaster, not only were the graphics and sound massively improved, a new controller scheme was also implemented for those who do not want to use the classic controls. With the new analog controls, the player can use the analog stick to press the direction they would like to go, as opposed to up always moving the character in the direction they are facing, etc. Players are able to switch between the two control schemes on the fly with the press of a button. With an internet campaign, released alongside the game, titled Raccoon City Contagion, players used social media to spread a virus throughout Raccoon City. Capcom stated that if fans were able to reach 100% infection, they would release free content for Resident Evil Remaster. On September 26, this goal was reached, and Jill and Chris's BSAA outfits were added to the game.
Shinji Mikami said that the remake is 70% different from the original.