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Saint Joseph High School first opened its doors to students on September 20, 1953 at 1441 North Michigan Street on the northern edge of South Bend.

The gym wing and cafeteria were still under construction and would not be completed until the following school year. The school, then known as Saint Joseph's High School, became the first consolidated, co-institutional Catholic high school in the South Bend area and drew students from its predecessor Catholic high schools: South Bend Catholic, Central Catholic, and Saint Joseph’s Academy.

The original high school was constructed under the leadership of Bishop John Francis Noll and the chairman of the Building Committee, Monsignor John Sabo. The parishioners of the South Bend and Mishawaka parishes gave generously to the construction project supplementing a large donation from the Bishop. These efforts allowed the school to be opened on 5.7 acres of land donated to the diocese by the Brothers of Holy Cross across from the campus of the University of Notre Dame.

From 1953 to 1968, Saint Joseph’s High School had separate divisions for boys and girls. In 1968, the school became coeducational. From the opening of the school through the 1970’s, the Sisters and Brothers of Holy Cross served as the nucleus of the faculty and administration. Their devotion and commitment to quality Catholic secondary education provided a foundation for the eventual transition to a lay faculty and administration. In 1980, Glenn Rousey became the first lay principal of the school, following the administration of Brother Francis Rotsaert, C.S.C. Diocesan priests continue to serve as school chaplains. 

The Forward in Faith Campaign kicked off in 2010 to begin the process of raising funds for a new facility to replace the aging building at 1441 North Michigan Street. In June 2011, ground was broken for a new Saint Joseph High School on the site of the former Saint Joseph Regional Medical Center. As the final year of classes at 1441 North Michigan Street progressed, so did work on the new building on Notre Dame Avenue. On the final day of the 2011-2012 school year, students, faculty, and staff celebrated the Saint Joe experience in its original home with t-shirts, a goodbye speech, and a blessing by longtime theology teacher, football coach and chaplain, Father Walter Bly.

Under the leadership of Principal Susan Richter, and as classes began for the 2012-2013 school year, the traditions begun in 1953 were transitioned into a new home just northeast of downtown South Bend. A new era in Saint Joseph High School history began on August 25, 2012 with the dedication of the new building by Most Reverend Kevin C. Rhoades, Bishop of the Diocese of Fort Wayne-South Bend. The Chapel of Saint Joseph, at the center of the facility, was dedicated on November 28, 2012. 

In succeeding years, the school has honored state champion athletic teams and athletes, hosted graduations, mourned the passing of students, won state Quiz Bowl championships, served the community with Joy of Saint Joe, and endured the challenges of the coronavirus pandemic. The neighborhood around Saint Joseph High School has experienced a revival, and new businesses continue to blossom within walking distance of the campus. Many attribute this economic development to the presence of Saint Joseph High School, which serves as an anchor to the northeast side of downtown.

In the spring of 2023, the Saint Joe community came together to evaluate the school nickname. Students, alumni, faculty, parents, and extended family contributed to the process. Led by the School Nickname Evaluation Committee, the school decided to retire the nickname Indians. Work will continue in the 2023-24 school year to choose a new nickname and mascot that will foster unity, pride, and school spirit into the future.

Through each transition and change, Saint Joseph High School has remained steadfast in carrying out its mission of  “transforming students in heart and mind, preparing them to serve God, the Church and the world.”