Thomas Brainerd was born in 1804 at Leyden, Lewis County, New York. In 1825 he was converted under the preaching of Charles G. Finney. In 1831 he graduated from Andover Theological Seminary, was ordained by the Third Presbytery of New York and went to the West under commission of the American Home Missionary Society. In the same year he became pastor of Fourth Presbyterian Church in the suburbs of Cincinnati and in 1833 he became associated with Lyman Beecher in Second Presbyterian Church, Cincinnati. He was editor of the Cincinnati Journal and Youth's Magazine from 1833 to 1836. In 1837 he was installed as pastor of Third (Old Pine) Presbyterian Church, Philadelphia, where he served for 30 years, until his death in 1866. Brainerd was moderator of the General Assembly, New School, in 1864.

Brainerd contributed to the daily and weekly press and to the Presbyterian Quarterly Review and published a Life of John Brainerd.