Originally called West Durham Elementary School, the oldest section of the current E.K. Powe was built in 1926 to begin replacement of a 1913 structure. It was renamed for Edward Knox Powe, general manager of the Erwin Cotton Mills in Durham, who was a philanthropist with great interest in public education.

A gymnasium was added to the school in 1949, one new wing in 1961 and another in 1975, with major remodeling done in 1991, 1994 and 2001. The school has a five-acre campus and its buildings enclose almost 95,500 square feet, with a student capacity of 408.