Jane Kaczmarek grew up in Milwaukee, Wisconsin. Her mother was a teacher and her father a Defense Department employee. She is the oldest child in her family. Jane was studying theatre at the University of Wisconsin. There, her friend Tony Shalhoub encouraged her to be a star. She enrolled at Yale with Shalhoub and performed in the Yale Repertory Company. She had some theatrical and film successes. Her roommate at Yale, Kate Burton, made a blind date between Jane and Bradley Whitford. They liked each other and after 2 years of dating, the two married.

Now, Jane Kaczmarek is well known for her role as "Lois" in Malcolm in the Middle. She was nominated for several awards.