Whitcomb started drawing illustrations for student publications while a student at Ohio State, and worked summers painting posters for a theater in Cleveland, Ohio. After he graduated, Jon found work making travel and theater posters and advertising illustrations. In 1934 he moved to New York City and joined with Al Cooper to found the Cooper Studio. Whitcomb was a pioneer in the switch from oil to gouache for illustrations. The different qualities of gouache compared to oil led to changes in the design of Whitcomb's illustrations. He zoomed in on people, usually pretty, young city women, and reduced the background to simple design elements. His new style of illustrations soon appeared in Collier's Weekly, Good Housekeeping and other magazines.
After the war Whitcomb produced a series of articles and sketches about Hollywood stars for Cosmopolitan, called "On Location with Jon Whitcomb". He continued to produce story illustrations and covers for magazines, including McCall's and Playboy. He wrote some short stories, two children's books, Coco, and Pom Pom's Christmas, and a book on glamour, All About Girls. He was one of the founding faculty of the Famous Artists School.