Barker made his Broadway acting debut in 1910 in the Shubert brothers production of "Mary Magdalene" written by Maurice Maeterlinck.

Acting was not Barker's forte and he trained as an assistant director until 1912 when he directed his first film, a twenty-minute western titled "On the Warpath" starring Art Acord.

The following year, with the United States still not involved in World War I, Barker co-directed the famous anti-war feature, Civilization.

During his career, Reginald Barker directed early stars such as Geraldine Farrar, William S. Hart, Sessue Hayakawa, Gladys Brockwell, Hoot Gibson, Willard Mack, and Myrna Loy.

Reginald Barker retired to Pasadena, California where he and his wife operated a gift shop until his death from a heart attack in 1945.