Pankow was born in St. Louis and raised in Chicago, the sixth of nine children. His mother was a homemaker and his father was an advertising salesman in technical publishing. His elder brother, James C. Pankow, performs in the successful recording group Chicago. John dabbled in drama during high school but didn't become serious about acting until he went to Northeastern Illinois University, where he majored in theater arts.
He left the university in his junior year after he attended a performance of David Mamet's "The American Buffalo" at the St. Nicholas Theater in Chicago. Inspired by the play, he enrolled in the theater's two-year theatrical training program in order to concentrate solely on acting.
While visiting a friend in New York City, Pankow auditioned for, and won, a role in a PBS film entitled "Life on the Mississippi." He went on to perform in several off-Broadway productions including "Scheherazade," "Aristocrats," "Italian American Reconciliation," "Hunting Scenes," "Ice Cream/Hot Fudge" and the New York Shakespeare Festival's "Two Gentlemen of Verona" and "Henry VIII." He subsequently made it to Broadway with "Serious Money," "The Iceman Cometh," and as Mozart in "Amadeus," one of his most notable roles to date. Last summer he reprised the role of Stefano in the runaway hit production of Shakespeare's "The Tempest" in Central Park.
Pankow has several motion pictures to his credit, including "A Stranger Among Us," "Mortal Thoughts," "Talk Radio," "To Live and Die in L.A." and "The Secret to My Success."
On the television side, Pankow has guest starred on such series as "Law and Order," "Spenser: For Hire" and "Miami Vice." After several guest spots in the first season of "Mad About You," he was signed as a cast regular.
Pankow is currently involved in developing projects for himself in the theater both as an actor and director. In his spare time, he enjoys cooking for his wife and their daughter. Having spent three months in Rome for a film shoot, he and his wife now consider themselves Italophiles. "We love to cook Italian," says Pankow. "At home, we go through vats of olive oil, garlic and other Italian staples."
Pankow and his wife live in Los Angeles with their 5-year-old daughter.