He was an accomplished stage actor working in Cincinnati, Ohio, before joining the Kalem Company motion picture studio in New York City in 1909. Hired by director Sidney Olcott for character actor roles, in the fall of 1910 he was sent to work with a film crew on the West Coast. In 1911, with Robert Vignola, he co-directed Ruth Roland in his first short film, Arizona Bill based on a script he had written. From there, Melford went on to direct another 30 films for Kalem Studios until 1915, when he was hired by Jesse L. Lasky to direct feature-length films for Lasky's Feature Play Company. That same year, Melford became one of the founding members of the Motion Picture Directors Association.