His upbringing in the "weird little" factory town and the backward eccentricities of his extended family lent themselves to his stand-up routine, which has been seen on HBO, Showtime, and Comedy Central, among other places. After high school, he studied communications and theatre at the University of Massachusetts at Amherst. He eventually moved to San Francisco to pursue a career in comedy. It was there he, along with fellow comedian Alex Reid, founded the San Francisco Comedy Condo in 1986. He now lives in Los Angeles.

Dana Gould has written 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 to Brimley's Quaker Oats advertisements). In one, he speaks of his hobby of dressing in a taffeta gown and filling his panties with oatmeal; in another, he brandishes a revolver through the window at children.

Gould also provided the voice for the title character in the Gex video game series.

Gould was featured in the film The Aristocrats, where, among other commentary, he presents an Amish version of the dirty title joke.

Gould is currently a producer for The Simpsons, on one episode of which he provided the voice of Don Knotts as Barney Fife (an impression that originated in his standup routine).