The couple married in June 2002 and had a daughter, Beatrice, two years later.
"Having tried exceptionally hard to make our relationship work given the daily pressures surrounding us, it is with sadness that we have decided to go our separate ways," they said in a joint statement released in London, the BBC reported.
The statement called the split "amicable" and the couple asked "for the sake of our baby daughter, that we be given some space and time to get through this difficult period."
On his Web site, McCartney, 63, lashed out at media coverage since he moved to the couple's farm leaving Mills, 38, and their daughter at their home in Hove.
"It's been suggested that she married me for the money and there is not an ounce of truth in this," he wrote. "I'm very sad to see that some insensitive people would choose a moment like this to spread these vicious rumors."
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