Chiklis was born in Lowell, Massachusetts, to Charlie Chiklis, a second-generation Greek American who runs a hair salon, and Kate, a hospital administrative aide from whom Chiklis has been described as inheriting his acting ability. Chiklis' paternal ancestors came from Lesbos Island. Chiklis grew up in Andover, Massachusetts and began entertaining his family with celebrity imitations when he was just five years old. As a child, Chiklis appeared in regional theater productions and earned his Actor's Equity card at age thirteen. He later attended Boston University College of Fine Arts, where he received his Bachelor of Fine Arts.

At age 20, Chiklis shaved his head to look like male-pattern baldness for the part of a 65-year-old man in You Can't Take It With You. Instead of using powder on his head (as he did on his face), he used greasepaint, and he failed to remove it properly at the end of each day. This killed the hair follicles on his head, essentially shaping his career in