The event was hosted by Geoff Keighley, creator and producer of The Game Awards, and was held to an invited audience at the Microsoft Theater in Los Angeles on December 9, 2021.

It featured musical performances from Imagine Dragons, JID, Darren Korb, and Sting, and presentations from celebrity guests including Reggie Fils-Aimé, Keanu Reeves, Ben Schwartz, and Ming-Na Wen.

Marvel's Guardians of the Galaxy was awarded Best Narrative, and Maggie Robertson won Best Performance for her role as Lady Dimitrescu in Resident Evil Village.

[4] Several safety protocols were put in place, including halving live attendance, mandating vaccines, and requiring face masks;[4] contingency plans were also established in case of unexpected COVID-19 variants or other issues.

[4] The Game Awards partnered with Spotify to produce a four-episode podcast titled Inside the Game Awards, hosted by Keighley and featuring IGN's Tina Amini, Giant Bomb's Jeff Gerstmann, and The Guardian's Keza MacDonald;[6] it was released weekly from November 22, 2021, with episodes focusing on the history of the show and musical performances, the 2021 nominees, and a post-show recap.

[13] Several days before the show, Alice O'Connor of Rock, Paper, Shotgun described the experience as "dead boring", which she said "seems perfectly fitting" for The Game Awards.

[16] After some criticism, Keighley stated Activision Blizzard would not be part of the ceremony outside of its nominated games, and wrote the show was committed to "work together to build a better and a more inclusive environment".

[22] Stanton and Bloomberg News's Jason Schreier identified the hypocrisy of following up Keighley's statement with the announcement of a game by Quantic Dream, a studio accused of a hostile workplace culture of racism, sexism, and misconduct.

[22][23] Keighley stated he wanted to ensure that spreading a message was balanced with the show's upbeat nature; he said using its platform to reprimand poor behavior is "always something worth thinking about, but it's not a referendum on the industry".

Xbox Game Studios[d] led the publishers with thirteen nominations, followed by Sony Interactive Entertainment and Electronic Arts with eleven, and Bethesda Softworks[d] and Square Enix with ten.

[27][33] Forza Horizon 5 and It Takes Two led the show with three wins each, followed by Deathloop, Final Fantasy XIV, and Kena: Bridge of Spirits with two awards each.

[47] TheGamer's Josh Coulson felt The Forgotten City, Lost Judgment, and MLB The Show 21 were unrecognized, and Keanu Reeves deserved a nomination for his role as Johnny Silverhand in Cyberpunk 2077.

[50] BBC's Steffan Powell considered the announcement of Wonder Woman the biggest surprise,[51] and Kotaku's Ari Notis found Have a Nice Death to be among the best reveals.

[18] Kellen Browning of The New York Times called the show "a victory lap of sorts for the video game community", identifying its crossover with other entertainment mediums.

[23] From The Washington Post, Nathan Grayson claimed the crowd stopped paying attention towards the end of the show, and Shannon Liao said some were leaving the venue at least ten minutes before the conclusion; Grayson described some of the presenters' speeches as "jokey, canned", and felt the show was missing "unexpected live moments that capture everybody's attention" like previous ceremonies.