From 1928 to 1929, he taught at the Forman Christian College in Lahore; from 1935 to 1951, he was the minister of Presbyterian churches in America, holding pastorates at churches in New York City and Albany, as well as serving as the Senior Minister of Pasadena Presbyterian Church in Pasadena for eleven years.
Blake became a trustee of Princeton Seminary in 1954.
Although an experienced and talented administrator, Eugene Carson Blake is best known for his forthright stand against racial segregation as well for his progressive stance on a number of issues affecting Protestant church denominations. In 1960, he preached a sermon calling for the unification of a number of major Protestant denominations into one separate church. This sermon is considered to be the impetus for the 40-year Consultation on Church Unionecumenical effort to unite ten mainline denominations.[5]