The Blurred Lines hitmaker began dating Patton when he was 14 and the high school sweethearts welcomed their first child, son Julian, in April, 2010.
However, despite cuddling up for the cameras at the Grammy Awards just last month (Jan14), the couple has decided to call it quits.
A statement issued to People.com reads: "We will always love each other and be best friends, however, we have mutually decided to separate at this time."
Thicke and Patton wed in 2005.
The couple's relationship has come under scrutiny in recent months after Thicke was photographed with socialite Lana Scolaro at a post-MTV Video Music Awards party in New York last September (13).
In the shot, Thicke appeared to be cupping the blonde's backside and she subsequently went public with claims that he didn't stop there, telling Life & Style magazine the singer hit on her, while Patton watched.
At the time, Patton's representative dismissed Scolaro as "just a girl looking for attention" and insisted the actress and her husband "aren't concerned" about the cheating rumours.