In 1839, after graduating from the Oneida Theological Institute in Whitesboro, Garnet moved to Troy, New York. He served as the pastor of the Liberty(Fifteenth) Street Presbyterian Church from 1864 until 1866, and during this time he became the first black minister to preach to the House of Representatives. He joined the American Anti-Slavery Society and frequently spoke at abolitionist conferences. One of his most famous speeches, "Call to Rebellion," was delivered August, 1843 to the National Negro Convention in Buffalo, New York.
In addition, by 1849 Garnet began to support emigration to Liberia. He was appointed president of Avery College in Pennsylvania, and became minister to Liberia in 1881, but he died two months later.