He served as a missionary in India for three years (1847–1850). He held pastorates at Lower West Nottingham, Maryland (1851–1855), Fredericksburg, Virginia (1855–1861), and Wilkes-Barre, Pennsylvania (1861–1864). In 1864 he accepted a call to the chair of systematic theology in Western Theological Seminary (later Pittsburgh Theological Seminary) in Pittsburgh, Pennsylvania. There he remained until in 1877 he was called to Princeton to be the associate of his father, Charles Hodge, in the distinguished chair of systematic theology. He took on the full responsibilities of the chair of systematic theology in 1878.