"With great sadness, we have decided to separate, after 18 years of love and shared history," the couple told the magazine in a joint statement.
"We will continue to be supportive of each other in every way possible moving forward," the statement said.
Hamm, 44, and Westfeldt, 45, were considered a model couple in Hollywood, staying together through Hamm's sky-rocketing fame during eight years on the hit AMC show "Mad Men." They first met in 1997.
In recent months they had battled rumors of a split and were last seen together publicly on July 22 in New York, People reported.
Hamm earned eight Emmy nominations for his dark portrayal as Don Draper on "Mad Men," which chronicled the advertising world and shifts in American society during the 1960s.
The series finale in May drew 3.3 million viewers.
Westfeldt is best known for writing and starring in the independent movies "Kissing Jessica Stein" and "Friends with Kids."
