The PlayStation 3 version of Resident Evil 5 was the top-selling game in Japan in the two weeks following its release, with 319,590 copies sold. It was the fastest-selling game of the franchise in the United Kingdom, and the biggest Xbox 360 and PlayStation 3 game release in the region. As of December 2014, Resident Evil 5 has sold 6.7 million copies worldwide for PlayStation 3 and Xbox 360, making it the bestselling Resident Evil game and the all-time bestselling Capcom game.
Resident Evil 5 received positive reviews. Although the game was praised for its graphics and gameplay, it was criticized for issues with its controls. Corey Cohen of Official Xbox Magazine complimented the game's fast pace, and called the graphics "gorgeous". It was praised by Joe Juba and Mark Miller of Game Informer, who said that it had the best graphics of any game to date and the music and voice acting helped bring the characters to life. However, Juba said that the inability to move and shoot at the same time seemed more "like a cheap and artificial way to increase difficulty than a technique to enhance tension." Chris Hudak of Game Revolution reviewed Resident Evil 5 favorably. Lamenting the game's departure from the survival horror genre, Hudak concluded that "the gorgeous environs, character models and overall visuals, and the adrenaline-soaked cooperative gameplay (wonky, stodgy Capcom controls and all) cannot be denied."
Adam Sessler of X-Play said that although the game's graphics were exceptional, the single-player artificial intelligence was hard to play through and he was disappointed in the controls taken (he felt) from Resident Evil 4.Edge praised Resident Evil 5's gameplay as exhilarating and frantic, echoing criticism of the control system. For IGN, Ryan Geddes wrote that the split-screen cooperative mode was very confusing but the game had a surprisingly high replay value. According to GameZone's Louis Bedigian, "The fact that Resident Evil 5 was worth playing through twice in one weekend shows how compelling the gameplay is, and how it's able to rise above a number of disappointing flaws." Criticizing the game's departure from survival horror and its inability to move and shoot (or stab), Brian Crecente of Kotaku blogged: "From beginning to end, this latest Resident Evil delivers a riveting and intense experience well worth the time spent playing it."
James Mielke of 1UP.com compared Resident Evil 5 to Gears of War 2. He criticized several inconsistencies in the game, such as the enemies' artificial intelligence and the ability to interact with objects and use cover. Mielke also criticized its controls, saying that aiming was too slow and noting the inability to strafe away from (or quickly jump back from) enemies. However, he concluded, "Despite the excruciating detail I've poured into describing the problems [Resident Evil 5] creates for itself, this is still a very fun game." Kristan Reed of Eurogamer also criticized aspects of the controls, such as the speed at which 180-degree turns were performed and difficulty accessing inventory. According to Reed, Resident Evil 5 felt a lot like past games in the franchise and was "just like any other third person action shooter".
Steven Hopper of GameZone rated the "Lost in Nightmares" DLC eight out of ten: "Even though the episode is pretty short, there is some good replay value here and the added multiplayer elements are a nice touch. All in all, this is a worthy investment for fans of the original game." Samuel Claiborn of IGN rated the "Desperate Escape" DLC seven out of ten: "Despite Desperate Escape's well-crafted action sequences, I actually found myself missing the unique vibe of Lost in Nightmares. The dynamic between Jill and Josh isn't particularly thrilling, and the one-liners, banter and endearing kitsch are kept to a minimum."Resident Evil 5 was nominated as Best Action Game at the 2009 IGN Game of the Year Awards.
The E3 2007 trailer for Resident Evil 5 drew criticism from various sources for containing supposedly racist imagery, specifically that of Caucasian protagonist Chris Redfield fighting and killing an all-black group of African enemies. Newsweek editor N'Gai Croal was quoted as saying "There was a lot of imagery in that trailer that dovetailed with classic racist imagery", commenting that the common counterpoint that no racist accusations were leveled against Resident Evil 4, which featured Spanish enemies, was inaccurate; "The imagery is not the same. It doesn't carry the same history, it doesn't carry the same weight. I don't know how to explain it more clearly than that." The second RE5 trailer, released in May 2008, introduced the character of Sheva Alomar, an African native and partner to Chris. In addition, the crowd of enemies pictured, while still predominantly black, also featured Hispanic, and Caucasian characters. It was rumored that the Sheva character and the mixed race enemies were added specifically to counter the accusations of racism, though producer Jun Takeuchi insisted that the accusations made absolutely no impact on development, and that the Sheva character had always been intended to be included.