Isabel Leighton began her career in the theater as an actress in the early 1920s. She went on to collaborate on writing six plays that were produced on Broadway, including Mercenary Mary (1925) and Spring Again (1941). In the 1930s and 40s, she wrote articles for various magazines and for the North American Newspaper Alliance. During World War II, she served as a naval correspondent. She was also the author, co-author, or editor of several books, including My Boy Franklin, as told by President Franklin D. Roosevelt's mother (with Gabrielle Forbush), and Where Away, with George Sessions Perry. She was the editor of The Aspirin Age, 1919-1941, a bestselling collection of articles by John Lardner, Howard Fast, and others. In the early 1950s, she was the moderator of a popular television program called "How Did They get That Way?" She served on the boards of several civic and philanthropic organizations, including the Menninger Foundation.