He was best known for his roles in City Slickers, When Harry Met Sally..., Good Morning, Vietnam, The Godfather Part II, The Freshman, Sleepers and Donnie Brasco.

His other television appearances included Room 222 and the pilot episode of M*A*S*H, portraying the character Boone (he had no lines).

His best-known roles include a colleague of Albert Brooks' film editor in Modern Romance; a talkative limo driver in This Is Spinal Tap; the jealous, comedically impaired Lieutenant Hauk in Good Morning, Vietnam; and a shifty assistant to Marlon Brando—a parody of Brando's Godfather role—in The Freshman.

Kirby refused to sign on for City Slickers II: The Legend of Curly's Gold unless script changes were made, and was subsequently replaced by Jon Lovitz.

[2] In 1991, Kirby made his Broadway debut when he replaced Kevin Spacey in Neil Simon's Lost in Yonkers.

He appeared on the HBO TV series Entourage in season 3, episode 4, "Guys and Doll", as movie mogul Phil Rubinstein.