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All nine members of the group (excluding Cappadonna) were featured in the game Wu-Tang: Shaolin Style, released for the PlayStation on October 31, 1999, as well as a special collector's edition controller.

Ghostface Killah and Yung Dirty Doucette, as well as collaborators Redman and Keith Murray, also play themselves in all three games in the Def Jam series, Def Jam Vendetta, Def Jam Fight For NY, and Def Jam: Icon.

Method Man is a huge fan of video games himself and has publicly stated that he loves playing SOCOM online with other PS2 users, and is even part of an online clan ("KMA/Kiss My Ass"). His Socom 2 name is "ICU". He has a fellow SOCOM player featured on a skit on his album 4:21.

A video game from Acclaim, 9Dragons, also sports the name Wu-Tang Clan in one of the ingame branches. In EA's Army of Two, Salem talks about Wu-Tang in the mission on China asking Rios who the best member is. Salem says it's RZA but he says Ghostface Killah is pretty good himself. In the ending cut scene, a reference is made when Salem says "Survey says?" and Rios replies "You're Dead,". The exchange referenced the lyric, "And the survey says? / You're dead!" from Wu-Tang Clan Ain't Nuthin' Ta F' Wit, from the album Enter the Wu-Tang Clan (36 Chambers).

Several tracks by Clan members and affiliates such as Method Man, Ghostface, Cappadonna, Trife, DJ Mathematics and others were featured in the 2006 game Saints Row. The video game of Afro Samurai, based on the cult TV series, was released in January 2009 for the PlayStation 3 and Xbox 360. Its soundtrack, like the show, was produced by the RZA.