Basil Manly, Jr. was born the eldest of eight children on December 19, 1825, to Basil Manly, Sr. and Sarah Murray Rudolph Manly. He was born in Edgefield District, South Carolina, but his family moved to Charleston soon after his birth. The Manly family moved to Tuscaloosa, Alabama in 1837 when Basil Manly, Sr. became president of the University of Alabama. Basil Manly, Jr. attended the University of Alabama and graduated in 1843. He left Alabama to attend the Newton Theological Institution in Massachusetts, but transferred to Princeton Seminary in New Jersey. He graduated in 1847.
After his ordination, Manly, Jr. held pastorates in Providence and Tuscaloosa, Alabama before becoming pastor at the First Baptist Church in Richmond, Virginia in 1850. He became principal at Richmond Female Institute in 1854, but he left in 1859 to become one of the four founding professors at the newly established Southern Baptist Theological Seminary in Greenville, SC. Manly, Jr. accepted the position as president of Georgetown College in Kentucky in 1871, but he returned to the Southern Baptist Theological Seminary (which had moved to Louisville, KY by that time), as professor of Old Testament Interpretation and Biblical Introduction in 1879. He remained in that position until his death from pneumonia on January 31, 1892.
Manly, Jr. married Charlotte Ann Elizabeth Whitfield Smith in 1852 and had 11 children with her before her death in 1867. He then married Hattie Hare in 1869, with whom he had six children. Manly, Jr. was highly gifted in music and wrote many hymns and poems, including the Baptist Psalmody he wrote with his father.