The 43-year-old actor cited irreconcilable differences and asked for joint custody of their 7-year-old son, Clyde, according to documents filed Friday in Los Angeles County Superior Court.
The couple, who appeared in the 2001 film "Lovely & Amazing," were married in November 1990 and separated in May 2005, the documents said. An after-hours e-mail to Keener's publicist wasn't immediately returned.
Mulroney's screen credits include "My Best Friend's Wedding," "The Wedding Date," and "Georgia Rule."
Photos: Star Splits
Keener, who has two Oscar nominations for supporting roles in "Capote" and "Being John Malkovich," has also appeared in "The 40-Year-Old Virgin" and "The Ballad of Jack and Rose."