A native of Philadelphia, Wood was raised in the Unitarian faith. His family moved to Cincinnati in 1827, where he came into contact with Bishop John Purcell, who assisted Wood's journey into Catholicism. After entering the Church in 1836, Wood served as a priest for the Diocese of Cincinnati until he was named coadjutor bishop of his native city in 1857. He succeeded John Neumann as bishop in 1860, and became Philadelphia's first archbishop in 1875.