In 2000, he starred in the Comedy Central series Strip Mall as Harvey Krudup, the husband of protagonist Tammi Tyler, who was played by Julie Brown.

[4] In July 1989, O'Heir appeared in the Chicago premiere of the Tom Griffin play The Boys Next Door at the Edgewater Theatre Center.

[5] Starting in 1990, O'Heir appeared in White Noise's Stumpy's Gang, a one-act black comedy play by Patrick Cannon.

[7] O'Heir played Frank Bubman, the janitor for a genetics laboratory whose job is to destroy the unsuccessful experiments, which are portrayed by puppets.

Mary Shen Barnidge of the Chicago Reader said of his performance, "The grotesquely ursine Jim O'Heir adds a new dimension to the role of the enfant terrible with his uninhibited and enthusiastic portrayal of Frank, who will break your heart even as he turns your stomach.

[11] Starting in 2000, O'Heir starred in a regular role in the Comedy Central series Strip Mall as Harvey Krudup, the unattractive husband of protagonist Tammi Tyler, who was played by Julie Brown.

[15] In November 2003, he made a guest appearance in the tenth season episode of Friends, "The One With the Birth Mother", where he played the manager of an adoption agency.

[11] On November 28, 2004, he appeared in the Boston Legal episode "Loose Lips", where he played a man fired from being a department store Santa Claus because he is a cross dresser.

That same year, he appeared on Jimmy Kimmel Live as real-life Toronto mayor Rob Ford, who had recently been involved in a crack-smoking scandal.