After his professional debut on Broadway in the 1999 revival of The Rainmaker, he was nominated for a Tony Award for his performance in a production of Who's Afraid of Virginia Woolf?.

He made his television debut on Law & Order in 1999 and had supporting roles in films such as Brokeback Mountain (2005), Revolutionary Road (2008) and Black Mass (2015).

[2] He attended Byram Hills High School in Armonk, New York, along with actors Sean Maher and Eyal Podell.

He graduated from Dartmouth College in Hanover, New Hampshire, in 1997,[3] where he majored in drama and Italian and was a member of the Sigma Phi Epsilon fraternity.

[4] As a young man in New York City, David Harbour frequented and participated in gambling at underground poker clubs, and attests that he personally knew the gangster who John Malkovich's character "Teddy KGB" was based on in the 1998 film Rounders.

Harbour is also known for his role as CIA Agent Gregg Beam in Quantum of Solace, as Shep Campbell in Revolutionary Road, and as Russell Crowe's source in State of Play.

[11] He most recently portrayed Alexei Shostakov / Red Guardian in the Marvel Cinematic Universe (MCU) film Black Widow (2021),[12][13] and will reprise the role in the upcoming Thunderbolts* (2025).

"[21] Harbour struggled with alcoholism in his past[22] and has been sober since he was 24, after hitting "rock bottom" as he faced homelessness, loneliness and thoughts of suicide.