Isham began as a playwright and later turned to novels, writing mainly historical romances and adenture novels set in various periods. Black Friday, for example, centers on the American financial crisis of 1869, while Under the Rose is set in 16th century Europe. His experiences in theater informed his first novel, The Strollers. Published by Bobbs-Merrill Company and its predecessor Bowen-Merrill Company, Isham's novels were illustrated by such artists as Harrison Fisher, William Thacher Van Dresser, Max J. Spero, and W. B. King. The critic H. L. Mencken wrote of his novel Half a Chance that it was "a brisk and entertaining story, with not too much reality in it," which well summarizes the general tenor of Isham's work.