Graduated in philosophy from Harvard University (1907), Locke was the first black Rhodes scholar, studying at Oxford (1907–10) and the University of Berlin (1910–11). He received his Ph.D. in philosophy from Harvard (1918). For almost 40 years, until retirement in 1953 as head of the department of philosophy, Locke taught at Howard University, Washington, D.C.

Locke stimulated and guided artistic activities and promoted the recognition and respect of blacks by the total American community. Having studied African culture and traced its influences upon Western civilization, he urged black painters, sculptors, and musicians to look to African sources for identity and to discover materials and techniques for their work. He encouraged black authors to seek subjects in black life and to set high artistic standards for themselves. He familiarized American readers with the Harlem Renaissance by editing a special Harlem issue for Survey Graphic (March 1925), which he expanded into The New Negro (1925), an anthology of fiction, poetry, drama, and essays.

Locke edited the Bronze Booklet studies of cultural achievements by blacks. For almost two decades he annually reviewed literature by and about blacks in Opportunity and Phylon, and from 1940 until his death he regularly wrote about blacks for the Britannica Book of the Year. His many works include Four Negro Poets (1927), Frederick Douglass (Douglass, Frederick), a Biography of Anti-Slavery (1935), Negro Art—Past and Present (1936), and The Negro and His Music (1936). He left unfinished materials for a definitive study of the contributions of blacks to American culture. His materials formed the basis for M.J. Butcher's The Negro in American Culture (1956).

A humanist who was intensely concerned with aesthetics, Locke termed his philosophy “cultural pluralism” and emphasized the necessity of determining values to guide human conduct and interrelationships. Chief among these values was respect for the uniqueness of each personality, which can develop fully and remain unique only within a democratic ethos.