An unidentified representative for Whitford confirmed the couple were ending their marriage of more than 16 years, People.com reported Friday.
"He hopes the media will respect their wish for privacy as they focus on their children," the representative said of Whitford.
Whitford and Kaczmarek are the parents of Mary Louisa, 6, George Edward, 9, and Frances Genevieve, 12. The couple married in August 1992.
Whitford played Deputy Chief of Staff Josh Lyman on the former NBC drama "The West Wing." Kacmarek is best known for playing Lois on the former Fox comedy "Malcolm in the Middle."