"After much soul searching and consideration we have made the decision to separate as a couple. As devoted parents, our first priority remains raising our children together with enduring love, respect and friendship," they said in a joint statement to People.
The former "Spider-Man" actor, 41, and the jewelry designer, 39, met in 2003 and were married in Hawaii in September 2007, by which time they already were parents to daughter Ruby, now 9. Their son, Otis, is 7.
Meyer is the daughter of Ron Meyer, vice chairman of NBCUniversal. Maguire hasn't been seen on screen since his Bobby Fischer movie, "Pawn Sacrifice," came out in September 2015, but he and Meyer have been busy dabbling in the political arena.
They made headlines in June 2015 when they hosted a fundraiser for Hillary Clinton, and in April, they welcomed President Obama and daughter Malia to their Brentwood home for a breakfast fundraiser for the Democratic Senatorial Campaign Committee.
Over the summer, Maguire was photographed hanging out on a yacht off Ibiza with bestie Leonardo DiCaprio.
Follow Christie D'Zurilla on Twitter @theCDZ.