A representative for the actress confirmed Monday that the pair are ending their 9-year marriage.
"We will always love each other and be best friends, however, we have mutually decided to separate at this time," the couple said in a statement to People, which was first to report the news.
Thicke, 36, and Patton, 38, met when they were teenagers. They had a son, Julian Fuego Thicke, in April 2010.
Thicke had a breakthrough last year with "Blurred Lines," which was nominated for several Grammy Awards. Patton has appeared in the films "Mission: Impossible -- Ghost Protocol," ''Idlewild," and "Precious."
Patton has also appeared in Thicke's music videos, including "Lost Without U" and "Love After War." She was the inspiration behind most of his music, and she appeared on the cover of his 2003 debut, "A Beautiful World."