The ground breaking ceremony for Toledo’s sixth Catholic high school took place on September 21, 1960, with Bishop George J. Rehring turning the first spadeful of earth. The school was named for Samuel Cardinal Stritch, Toledo’s second bishop during the years of 1921 through 1930.

A twenty-acre site was chosen for the East Side area’s first co-institutional high school. One side of the school was reserved for boys’ classes, the other for girls’, with co-educational classes being held in the center sections. (The separate wings were integrated in 1971 when all classes became co-educational.) The first principal was Monsignor Michael Walz, who initiated the “Stritch Family” concept.

Succeeding principals have been Rev. John A. Thomas, Rev. Frank Nieset, Sister Louis de Montfort, Rev. Frank Murd and Rev. Robert J. Yeager, Ed.D. In 1997 the Bishop appointed the Rev. John Stites as the first President of the school. Mr. Timothy Mahoney became the first lay person to be assigned as principal of the school.

In 2004, Father David Reinhart was appointed president of Cardinal Stritch High School. During his time at Cardinal Stritch High School, Father Reinhart has led an unprecedented upgrade to campus facilities and has given vision to a new way of thinking about Catholic education in light of a theology of stewardship. Under Father Reinhart's leadership, Cardinal Stritch High School has been recoginized as one of the top 50 Catholic high schools by the National Catholic High School Honor Roll.

The high school has also taken on leadership rolls in the creation of the Live It initiative and the Kateri Education Project, a regional study of Catholic education. Most importantly, the school has clarified its vision as being a place that forms disciples of Jesus Christ. They have adopted a service learning program, "Stewards of Stritch", moved from monthly to weekly Mass for all of its students, and helped to draw the attention of the entire high school community toward the Eucharist as the source and summit of our faith and therefore, at the center of the school.