Twelve authors were in the running for the 60,000 pound (68,000 euro) award.
Roth is America's most decorated living novelist.
The Man Booker prize was first presented in 2005, and is given every two years
The 78-year-old Roth, who could not travel to Sydney for the award ceremony because of back problems, said it was a great honour to be recognised.
"One of the particular pleasures I've had as a writer is to have my work read internationally despite all the heartaches of translation that that entails," he said in a statement. "I hope the prize will bring me to the attention of readers around the world who are not familiar with my work. This is a great honour and I'm delighted to receive it."
Roth is one of the world's most prolific writers, dealing with themes such as Jewish-American identity, the line between autobiography and fiction and 20th-century US history. The humour present in much of his early work has given way to more sombre examinations of social questions and the question of death in his later output.
He is best known for his 1969 novel Portnoy's Complaint, and for his trilogy comprising the Pulitzer Prize-winning American Pastoral (1997), I Married a Communist (1998) and The Human Stain (2000).
The Man Booker International Prize is different from the better known Man Booker Prize, which is given annually to writers from the British Commonwealth and Ireland, in that it highlights one author's overall body of work.
It has previously been won by Albanian author Ismail Kadare in 2005, Nigeria's Chinua Achebe in 2007 and Alice Munro of Canada in 2009.
This year British thriller writer John le Carré asked that his name be withdrawn from the shortlist because "I do not compete for literary prizes".
The 2011 prize was the first to include Chinese authors in Wang Anyi, whose Shanghai novels include The Song of Everlasting Sorrow, and Su Tong, writer of Raise the Red Lantern: Three Novellas.
Indian-Canadian Rohinton Mistry and US writer Anne Tyler were also in the running.