DC Comics conducted a deal with publisher Acclaim Entertainment in June 2003 to produce games based on the 100 Bullets comic book. 100 Bullets was in development by Acclaim Studios Austin. The game's art was designed by Eduardo Risso, who also worked on the comic. The character of Snow Falls was created by the comic's creator Brian Azzarello. A stated goal of Acclaim's was to "challenge players to 'think before they shoot' and allow them to explore the moral implications of their actions". It was featured at the 2004 E3 convention. It was slated to release in October 2004, but was cancelled following Acclaim Entertainment's financial troubles.

A deal established between Warner Bros. Entertainment and D3 Publisher of America in May 2006 gave D3 the rights to adapt the comic into video games on home game consoles, handheld game consoles, and PCs. Its first release was planned for Q3 2007. Careen Yapp (Vice president of licensing and business development for D3) was positive about the project and noted that the publisher would try to "maintain the authenticity consumers demand". It was planned for release on Game Boy Advance, Nintendo DS, PC, PlayStation 3, Xbox 360, PlayStation Portable, and Wii. D3 did not comment on the project for years; a rumour surfaced when a "GameStop insider" stated that it would release in 2009 on the PlayStation 3 and Xbox 360. A spokesperson for D3 could not give anymore details due to the game being built from the ground up. All releases of this game excepting the Xbox 360 and Wii versions (which are labelled TBA or "to be announced") have been cancelled. D3 no longer features 100 Bullets on its list of video games.

When asked for news on the project, Azzarello noted that it was dead and if it was picked up, he expected to be a consultant. He expressed optimism that the comic could be adapted to a video game. He stated in an interview that he was never looking to adapt 100 Bullets into a video game and only took the opportunity to make one to "see what happens". He felt that the story didn't adapt well to a video game. He later noted that while there was "still talk", he didn't expect that it would happen anymore, also stating that it was "a little too intense to get off the ground".

Both the idea of an adaptation of 100 Bullets and the demo version of the Acclaim Entertainment adaptation have been met with positive reception. Brad Shoemaker's hands-on impressions for GameSpot of its E3 2004 build were generally positive. He praised its improvements over the previous build he saw, such as destructible environments and more finalized art. He felt that it was a good comic to adapt to a video game. Ricardo Torres found the human shield mechanic entertaining and felt that the graphics were well-done. Jeremy Dunham felt that its faithfulness to the comic's style was "dead on". Siliconera's Spencer felt thankful that the project was revived by D3 and called the comic series a "great property". Ben Reeves expressed hope that the D3-produced video game would fare better than the Acclaim-produced one. Justin McElroy expressed disappointment that the two adaptations of 100 Bullets have not had any luck at getting a release.