Byrne was ordained to the Roman Catholic priesthood by Archbishop John J. Glennon on June 10, 1933, for the Roman Catholic Archdiocese of Saint Louis after attending St. Louis Preparatory Seminary and Kenrick Seminary.
[5] On May 21, 1954, Pope Pius XII appointed Byrne auxiliary bishop of the Roman Catholic Archdiocese of Saint Louis, and he was consecrated on June 29, 1954.
[8][1] Upon Mark Carroll's retirement on February 15, 1963, Byrne became the apostolic administrator sede plena (transl.
[5] The episcopal advisor of the National Laywomen's Retreat Movement, he was seen as a "staunch defender" and proponent of the rights of women in the church.
[11][5] Pope Paul VI appointed Byrne as coadjutor archbishop of the Saint Paul-Minneapolis archdiocese on July 31, 1967.