In a joint statement, Vanessa and Donald Trump Jr. have confirmed they are divorcing.
"We will always have tremendous respect for each other and our families. We have five beautiful children together and they remain our top priority," the couple said.
Vanessa filed divorce papers late Thursday in New York City.
Before she married into the Trump clan 12 years ago, Vanessa was a fashion model. She also tried acting, appearing briefly in films like Something's Gotta Give, with Jack Nicholson and Diane Keaton.
President Trump introduced the pair at a fashion show in 2003. Two years later, they were married at Mar-a-Lago.
During Trump's White House campaign and afterward, she reportedly was uncomfortable under an intense media spotlight. She was also said to be fed up with the relentless attention.
Last month, she was shaken by a threatening letter she opened that contained a white powdery substance. She was taken to a hospital, but testing on the powder determined it was actually cornstarch.