In 1834, his older brother Michael, former Vice-Rector of the Pontifical Irish College in Rome, was serving as chaplain at for the convent of the Presentation Sisters in Doneraile.

From there he completed his studies at the Pontificio Collegio Urbano de Propaganda Fide in Rome, where he was ordained a priest in 1845.

In 1872, he became pastor of St. Dominic's in Holmesburg, Philadelphia and served as chaplain to the nearby Society of the Sacred Heart at their motherhouse at Eden Hall in Torresdale.

It became the duty of the new vicar to provide for the growing needs of the faithful, and the yearly statistics of the vicariate show how successful were his labours.

Bishop O'Connor also introduced into his jurisdiction the Franciscan Fathers, the Poor Clares, the Religious of the Sacred Heart, the Benedictines, and the Sisters of Providence.

Bishop O'Connor died shortly before noon on May 27, 1890, at the age of sixty-seven, after having been in failing health for about a year.