Dana Gould began performing comedy onstage at age 17. After high school, he studied communications and theatre at Framingham State College, but after a year moved to San Francisco to pursue a career in comedy. It was there that he, along with fellow comedian Alex Reid, founded the San Francisco Comedy Condo in 1986. Gould wrote and performed on The Ben Stiller Show; one such sketch features Gould as Otto, Cupid's twisted brother, whose arrows convince a young man to fall madly in love with an elderly woman. Another series of sketches features a heavily disguised Gould as Wilford Brimley advertising "Grady's Oats" (a parody of Brimley's Quaker Oats advertisements). He also appeared in an episode of MADtv as Newt Gingrich and on one episode of Seinfeld ("The Junk Mail") as "Fragile" Frankie Merman, Jerry's childhood friend. He co-created and was executive producer on Super Adventure Team. In addition, Gould's stand-up material was featured in Comedy Central's animated series Shorties Watchin' Shorties. In 1998, Gould appeared in the episode "Supermarket Story" of The King of Queens. Gould wrote for The Simpsons for seven years (2001–2007), and served as co-executive producer on seasons 14 through 18 (2002–2007). During his time with the show, Gould provided voice work on three episodes, including a 2005 episode on which he provided the voice of Don Knotts as Barney Fife–an impression that originated in his stand-up routine. Though Gould left the show to focus on his own screenwriting, he has returned three times to voice characters.

Gould had a featured cameo in Girls Will Be Girls. He was also featured in The Aristocrats, where, among other commentary, he presents an Amish version of the eponymous joke. His short films, Last Man On Earth, Break On Through With J.F.K., A Night On Java Island, and Soul Mates are also available for download on his site. Except for the latter, all feature Gould in acting roles. 2009 saw the release of his new stand-up special, Let Me Put My Thoughts In You, on Shout! Factory. Gould provided the voice for the title character in the U.S. versions of the Gex video game series and the U.K. version of the first game. Gould, with his frequent writing partner Rob Cohen, wrote the majority of the jokes for the games. Gould also voiced Hi Larious in Father of the Pride. He was a regular contributor to the Adam Carolla Radio Show where he did impressions of Huell Howser. He appears occasionally on The Adam Carolla Show podcast. The first episode of Gould's own podcast The Dana Gould Hour was made available on iTunes on January 31, 2012. Recurring guests include comedians like Eddie Pepitone, and each episode revolves around a singular theme.