
Grant's publicist Robert Garlock said the split was amicable and the decision had been taken in the last few days.
Grant, 46, and Khan, 33, the daughter of Sir James Goldsmith, began dating after the end of her marriage to former Pakistani cricketer Imran Khan.
Music and Lyrics, Grant's latest film, which also stars Drew Barrymore, topped the UK box office chart this week.
The split comes days after Grant and Khan, who has two children, attended US and UK premieres of the film.
A spokesman for Grant and Khan said: "It is an entirely amicable split but both regard it as a private matter and will not be making any further statements."
Grant, who shot to fame in romantic comedies including Four Weddings and a Funeral and Notting Hill, has never been married.
He previously had a long-standing relationship with actress and model Elizabeth Hurley.
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