After serving in World War I, he returned to Baltimore where he began working as a reporter. He first worked for the Baltimore American and then for the Baltimore Sun until 1923.

After a time in New York, Cain moved to Hollywood. There he tried screenwriting, but was more successful when he began to write fiction. His two most well known novels are The Postman Always Rings Twice, published in 1934 and Mildred Pierce . Both were best selles and were made into movies. Cain returned to Maryland in 1948, settling in Hyattsville.

In his later years Cain occupied himself with the study of Shakespeare's sonnets and classical music - his fourth wife was the opera singer Florence Macbeth Whitwell. In 1970 he was named a Grand Master by the Mystery Writers of America. James M.Cain died on October 27, 1977, in Hyattsville, Maryland.

The University of Maryland has put together a James M. Cain collection which is one of its treasures. All of the hardbacks are first editions, and all have been signed by the author.