Notre Dame High School is an all-girls private Catholic college preparatory secondary school that has been providing an excellent education to young women for more than 90 years. The high school is a sponsored ministry of the School Sisters of Notre Dame – Central Pacific Province and is adjoined to their motherhouse, which is home to more than 60 sisters.

Notre Dame High School lives by its mission statement. Responding to the mission of Jesus and the charism of the School Sisters of Notre Dame, the Catholic community of NDHS empowers its students to become confident, compassionate Christian women leaders. Notre Dame High School provides a strong college preparatory program to young women through an environment of differentiated instruction. Notre Dame High School's common vision is to educate students and promote lifelong learning, faith and service.

Notre Dame High School’s roots reach back to 1895 when the School Sisters of Notre Dame founded Sancta Maria in Ripa High School, a school for young women who were interested in entering the School Sisters of Notre Dame and had not completed their high school education. In 1925, Sancta Maria received its first accreditation from the North Central Association through the University of Missouri as a four-year high school.

In 1934, in response to parental requests for a high school for young women in South St. Louis, Sancta Maria became Notre Dame High School, open to both lay students and aspirants. The first class numbered 30 young women. Classes were held in the motherhouse of the School Sisters of Notre Dame.

In 1953, the gym and a meeting room were built, followed in 1955 by the L-shaped high school building still in use today. Classes were moved out of the motherhouse into the new high school. The history of Fall Festival began with the Penny Party in the 1950s. Each of the four classes collected pennies to have their class aspirant crowned the Penny Queen.

In the late ’50s and early ’60s, the school served a student body of more than 500 young women. The 1960s brought many changes to the curriculum, including advanced college credit courses, a full-time guidance department, the inauguration of modular scheduling and more extensive elective courses.

In 1971, Notre Dame High School’s faculty and administration recognized the need to change from a traditional teacher-centered approach to education to a more student-centered instructional system. Differentiated Instruction began, offering students an individualized approach to education with a current 10:1 student-teacher ratio.

With the closing of Notre Dame College in 1977, the high school acquired the use of a second building. Romana Hall was named after S. Romana Hechenberger, SSND who served as principal of NDHS from 1950-1967. The building houses the science and fine arts departments.

In 1996, a new corporation called Notre Dame Ministry Corporation was formed. Notre Dame High School is now a part of that corporation. In 1999, under administrator S. Georgiann Wildhaber, Notre Dame High School built a new road into the SSND Ripa Complex providing NDHS with a safer and more attractive approach to the school.

Today, 100% of graduates pursue higher education. Notre Dame High School's 8,000+ alumnae live and work in 46 states and 8 countries and comprise 39.5% of the current faculty and staff.