Albert Barnes graduated from Hamilton College, Clinton, New York, in 1820, and from Princeton Theological Seminary in 1823. Barnes was ordained as a Presbyterian minister by the presbytery of Elizabethtown, New Jersey, in 1825, and was the pastor of the Presbyterian Church in Morristown, New Jersey (1825–1830), and of the First Presbyterian Church of Philadelphia (1830–1867).
He held a prominent place in the New School branch of the Presbyterians during the Old School-New School Controversy, to which he adhered on the division of the denomination in 1837. In 1836, he had been tried (but not convicted) for heresy, mostly due to the views he expressed in Notes on Romans of the imputation of the sin of Adam, original sin and the atonement; the bitterness stirred up by this trial contributed towards widening the breach between the conservative and the progressive elements in the church. He was an eloquent preacher, but his reputation rests chiefly on his expository works, which are said to have had a larger circulation both in Europe and America than any others of their class. Of the well-known Notes on the New Testament, it is said that more than a million volumes had been issued by 1870. The Notes on Job, the Psalms, Isaiah and Daniel were also popularly distributed. The popularity of these works rested on how Barnes simplified Biblical criticism so that new developments in the field were made accessible to the general public.