Vrenna has also worked on music for several video games, including Call of Duty: Advanced Warfare, Doom 3 (as producer with Clint Walsh), Quake 4, American McGee's Alice, its sequel Alice: Madness Returns, Enter the Matrix, Sonic The Hedgehog, Area 51, and Need for Speed: Most Wanted. In 2004, he started soundtrack work on Tabula Rasa, a massive multiplayer online game. He also helped compose the theme song to the animated series Xiaolin Showdown.
Vrenna was chosen to take over the drumming responsibilities for Marilyn Manson after Ginger Fish was injured in 2004 during the Lest We Forget tour. He then replaced Madonna Wayne Gacy as the permanent keyboardist for Marilyn Manson. Vrenna co-produced the albums The High End of Low (2009) and Born Villain (2012). In April 2011, following the departure of Marilyn Manson's drummer Ginger Fish, Chris Vrenna was announced to be his official replacement. However, in November 2011, it was announced that Vrenna had parted ways with the band in order to focus on scoring movies and video games.