Cruise, 38, has received three Oscar nominations, for Magnolia, Jerry Maguire and Born on the Fourth of July. He was previously married to actress Mimi Rogers.
The couple have blamed the pressures of working apart, but the separation is said to be amicable.
They met on the set of the film Days of Thunder in 1990, and married the same year.
The highly successful pair starred in several films together, including Stanley Kubrick's erotic thriller Eyes Wide Shut in 1998 and the Ron Howard film Far and Away.
But recently they have been working on separate projects.
"Citing the difficulties inherent in divergent careers, which constantly keep them apart, they concluded that an amicable separation seemed best for both of them at this time," spokesman Pat Kingsley said.
Eleven year itch?
The couple "stressed their great respect for each other, both personally and professionally," he said.
Cruise, 38, has received three Oscar nominations, for Magnolia, Jerry Maguire and Born on the Fourth of July. He was previously married to actress Mimi Rogers.
He also appeared in films Top Gun and Mission Impossible, as well as Rain Man, which co-starred Dustin Hoffman as his autistic brother.
Kidman, 33, who has dual Australian and US citizenship, starred in Batman Forever and The Portrait Of A Lady, as well as the acclaimed To Die For.
The news of their unexpected separation will have surprised Hollywood, where they were seen as having a solid marriage.
Kidman said in an interview in 1998 that the couple was past the "seven-year itch" in their relationship.
Custody
"When you're loved for your flaws, that's when you really feel safe," she said.
In the same year she said: "I can't say what our journey is going to be. But it will be a hell of a journey.
"And I see myself as an old woman and he's an old man and we're married. I do see that."
Cruise and Kidman have two adopted children, Isabella and Connor. It is not clear who will have custody of them.
Three years ago the Daily Express newspaper was ordered to pay the couple more than £100,000, as well as legal costs, for unsubstantiated claims about their marriage.
The paper donated the money to a charity.
The United Nations agency which protects trademarks and patents, the World Intellectual Property Organisation, ruled against American John Zuccarini.
He had registered the domain names nicholekidman.com (sic) and nicolekidmannude.com.