While still a student, Thurman began his public career by becoming a young movement leader in the 1920s with the YMCA as well as various churches and colleges campuses. He went on to serve at Howard University as professor of Christian theology and dean of Rankin Chapel from 1932-44, where his work as an ecclesiological and liturgical innovator was widely acclaimed. During this period, Thurman also led a "Negro Delegation of Friendship" to South Asia in 1935-36. It was the first delegation of African Americans to meet Mohandas Gandhi. His conversations with Gandhi strengthened his Christian commitment and broadened his theological and international vision. Thurman's Gandhian ideals assumed clearest form in his most famous book, Jesus and the Disinherited (1949), which deeply influenced Martin Luther King, Jr., and other civil rights leaders.

Thurman left Howard University in 1944 to help establish the first racially integrated, intercultural and interfaith church in the United States, the Church for the Fellowship of All People, located in San Francisco. From 1953-65, he served as professor of spiritual resources and dean of Marsh Chapel at Boston University, the first black man to occupy the post of dean at a traditionally white university.

He continued his ministry as director of the Howard Thurman Educational Trust in San Francisco from its founding in 1965 until his death in 1981. Thurman's vision of a "friendly world underneath friendly skies" continues his rich legacy of the written and oral word.