In addition to his commercial and video game voice-over work, he also does many voice-overs for the American Bridge 21st Century PAC and the non-profit progressive research and information center Media Matters for America.

Douglas performed on stage in the San Francisco Bay Area in the late 1970s and early 1980s, moving to Los Angeles in 1985 to study at the Estelle Harman Actors Workshop. In Los Angeles, he co-founded the improvisation troupe Section Eight, and was a member of Theatre of NOTE. In 1996, he landed a small role in Boston Common, an NBC pilot. When the show was picked up for a season he returned in ten additional episodes as the character D.C., the antagonist to Hedy Burress's character.

Douglas has also worked with The Asylum since 2002, having appeared in seven films, including Sharknado 2 (as "Bud" the sewer worker) and Isle of the Dead (as "Aiden Wexler" - another Resident Evil inspired role) on the SyFy network.

That same year, Douglas wrote, produced and starred in Falling Words, his first festival film short. In subsequent years he wrote, produced and directed The Eighth Plane, an anti-Scientology gangster film short and Freud and Darwin Sitting in a Tree, about cousin marriage and Lewis Henry Morgan. In 2005, Douglas's film short, Duck, Duck, Goose!, played film festivals worldwide and received awards for the Best Short from the Seattle's True Independent Film Festival (STIFF) and Best Actor from the Trenton Film Festival.

Voice over credits include The Master in the Buffy the Vampire Slayer video game, Albert Wesker in Resident Evil: The Umbrella Chronicles, Resident Evil: The DarkSide Chronicles, Resident Evil 5 and Marvel vs. Capcom 3: Fate of Two Worlds, Raven in Tekken 6, AWACS Ghost Eye in Ace Combat 6: Fires of Liberation, Commandant Alexei in Tales of Vesperia, Legion in Mass Effect 2 and Mass Effect 3, Grimoire Noir in Nier, Hector Birtwhistle (H.B.) in Xenoblade Chronicles X, as well as several national campaigns (including the GEICO Celebrity campaign from 2006–2008, the McDonald's Be the Sizzle campaign from 2009–2010, Radio Shack's Holiday Hero campaign in 2010, and a 2014 Experian spots featuring Douglas and SpongeBob SquarePants voice Tom Kenny as computers). Douglas is the voice of Chase in The Hub's Transformers: Rescue Bots, Dylas in Rune Factory 4. Douglas also voices Azrael in the video game BlazBlue: Chrono Phantasma and Coburn in Ubisoft's racing game The Crew.

His 2009 CGI film short, The Crooked Eye starring Fay Masterson and narrated by Academy Award winner Linda Hunt, played festivals around the world and won awards for Best Narration (STIFF), Best Screenplay (HDFest - New York) and Best Animated Short (Red Rock Film Festival)

In April 2010, Douglas came under fire from the Tea Party movement for a phone call he made to Freedomworks in which he left an inflammatory voice mail. A day later GEICO dropped him from the new "shocking news" series of internet commercials that were in post-production. This led to some debate in the voice-over community about whether announcers were public figures. Douglas responded by producing a mock Tea Party PSA for YouTube that was subsequently broadcast on Joy Behar's HLN show with Douglas as a guest.

In November 2011, D.C. Douglas tweeted out a quote from a Tower Heist Q & A at the ArcLight Hollywood where Brett Ratner made a disparaging remark about homosexuals. The Hollywood Reporter subsequently reported Douglas' tweet as the beginning of a controversy which led to Ratner stepping down from the 2012 Oscars.

In 2013, Douglas was cast as a serial killer in Apocalypse Kiss and changed his appearance to look similar to Resident Evil villain Albert Wesker. The producers were fans of the video game franchise.

In 2016 he wrote, edited and directed an animated short, Ginger & Snapper, with Rachael Leone, an Animator he met on Twitter. Voices include Lacey Chabert and several voice actors known for their work in the Resident Evil video game franchise. They include Steve Blum, Liam O'Brien, Laura Bailey and Roger Craig Smith.

In 2017, D.C. launched MSM Breaking News!, an internet cartoon series satirizing the Donald Trump presidency and the Robert Mueller investigation into the Russian interference in the 2016 United States elections. A typical episode was written by D.C. Douglas and produced within ten hours by D.C. and his Animator, Rachael Leone. Guest voice over actors have included Steve Blum, Maurice LaMarche, Mary Elizabeth McGlynn, Todd Haberkorn, Mark Meer, and many others.