After graduation, Chiklis moved to New York City with high ambitions, but he struggled for several years before being cast the role of John Belushi in the controversial biopic Wired in 1989. The film was panned in general and flopped at the box office, but Chiklis received good reviews for his performance. He also guest starred in several popular television series such as Miami Vice, L.A. Law, Murphy Brown, and Seinfeld alongside bit parts in films like Nixon.

The Commish was Chiklis's first acclaimed and successful role. In the family-friendly police comedy/drama, Chiklis played Anthony "Tony" J. Scali, a police commissioner in a small city in upstate New York. A stern but lovable father figure, Chiklis's character had an easygoing style, smart wit, and an unorthodox approach to parenthood and police work. After The Commish, Chiklis starred in the short-lived and critically-panned NBC sitcom Daddio. After playing Curly Howard in a television movie about the Three Stooges, Chi