Some of his most prominent roles include appearances in the TV series ER as Dr. Archie Morris, Party of Five as Will McCorkle, Band of Brothers as Technical Sergeant Donald Malarkey, and the animated sitcom American Dad!, voicing Steve Smith.

As a singer, Grimes is best known for co-writing and performing the soft rock single "Sunset Blvd", which peaked at number 18 on Billboard’s Adult Contemporary chart in April 2005.

He is the uncle of Camryn Grimes, who is known for her roles as Cassie Newman and Mariah Copeland on The Young and the Restless.

In 1984, at the age of 13, he co-starred with Mickey Rooney in a made-for-TV holiday movie titled It Came Upon the Midnight Clear.

In 1988, he appeared with Dwayne Hickman, Connie Stevens, and her daughter Tricia Leigh Fisher in the TV movie Bring Me the Head of Dobie Gillis; Grimes, Hickman, Stevens, and Fisher also appeared on the All-Star Super Password Special with Bert Convy.

He is also known for his 1987 recurring role on Who's the Boss as Alyssa Milano's character's love interest, Chad McCann and his regular appearances in the 1994–2000 series Party of Five as Will McCorkle.

The character initially provided comic relief, but grew over the years, becoming central to several episodes and story lines in the series' final seasons.

[7] Grimes' film credits include the dark comedy Who's Your Monkey and Ridley Scott's Robin Hood with Russell Crowe and Cate Blanchett.