The history of Holy Trinity dates back to 1893, when Bishop Northrop dedicated the first Catholic Church in Orangeburg. Holy Trinity was elevated to full parish status in 1917 when Father James Quinn came to Orangeburg as the first resident pastor. The rectory was built in 1922 and in the 1930’s the Redemptorist Fathers took charge of Holy Trinity and replaced the small wooden church on Amelia Street with a brick structure.
A mission for African Americans began in 1939, and in 1940 a combination church, school, and convent was erected on Treadwell Street. Four days before it was to be dedicated it was burned down. Nevertheless, it was rebuilt and dedicated as Christ the King by Bishop Emmet Walsh on October 18, 1942. One year later the Oblate Sisters of Providence came to develop and staff the first and only Catholic Church in the county.
In 1966, a catechetical center and social were erected on Riverbank Drive. Bishop Ernest Unterkoefler merged Christ the King and Holy Trinity. Christ the King church was closed and the school relocated in the new catechetical center and renamed Holy Trinity School. Mass for the entire parish was held in the cafeteria of the catechetical center.
In 1984, a capital campaign began to raise funds for a new church. Bishop David Thompson dedicated the new church on December 10, 1992. That same year the Orangeburg Mission returned to the Diocese of Charleston after over 50 years of Redemptorist care.
In 2012, St. Andrew parish in Barnwell, St. Theresa parish in Springfield, and St. Mary Mission in Allendale were merged with Holy Trinity parish in Orangeburg with Holy Trinity as the administrative hub for the group. Holy Trinity currently serves over 375 households.