On September 2, 1958, Holy Family High School was established in Columbus, Georgia to fill the void in local Catholic education facilities. The Most Reverend Thomas J. McDonough, Bishop of the Diocese of Savannah, and Reverend Monsignor Herman J. Deimel decided to honor the late Holy Father, Pope Pius XII, Eugenio Pacelli. Consequently, the name of the school was changed and Pacelli was born. Since its establishment in 1968, Pacelli High School has been owned and operated by the Catholic Diocese of Savannah under the direct supervision of the Bishop and Superintendent of Schools. Beginning July 1, 1997, St. Anne Parish assumed ownership and governance of Pacelli High School.

The mission of Pacelli High School is "to provide an excellent education in a Catholic Christian environment to every student entrusted to our care." This mission is implemented through a faith-based curriculum which includes daily prayer, a broad selection of college prep academics, athletics, and other co-curricular and extra-curricular programs. The school is accredited by the Southern Association of Colleges and Schools, and is an active member of the National Catholic Education Association, the Georgia High School Association, and is administered within the framework of the Catholic Diocese of Savannah. The student body is composed of students from a diversity of many different faiths, which strengthens the school and adds to its distinctive character.