She is best known for her role as Lois, the mother in the popular sitcom Malcolm in the Middle.
Kaczmarek majored in theater at the University of Wisconsin where she met future actor Tony Shalhoub. She later enrolled in Yale with Shalhoub and was a part of its theater company. She has had several Broadway hits, including Lost In Yonkers and has occasionally guest starred on The Simpsons, providing the voice of Judge Constance Harm.
As of the 2005 Emmy Awards, Kaczmarek is a six-time nominee for Oustanding Lead Actress in a Comedy Series, and has been nominated from 2000-2005 for her role as Malcolm's mother. However, she is still waiting for her first Emmy win.