"I sadly announce that Jemima and I are divorced," Khan said in a brief statement issued by his Pakistan Justice Movement party.
The divorce ends months of speculation, particularly in the British media, about the future of the future of the duo, also called Pakistan's "first couple."
"This was a mutual decision and is clearly very sad for both of us," Khan said.
Media reports had said that his wife did not approve of Khan's political activities, particularly after his dismal performance in the two previous elections.
Khan became famous after winning the 1993 cricket world cup for Pakistan and gained more respect by building a multi-million dollar charity hospital in his hometown of Lahore.
"Whilst Jemima tried her best to settle here, my political life made it difficult for her to adapt to life in Pakistan," Khan acknowledged.
Jemima, 30, is the daughter of the late Anglo-French billionaire James Goldsmith. She converted to Islam and immersed herself in Pakistani culture after marrying Khan in 1995.