The school was established after fundraising by the Catholic parishes of Westchester County, under the leadership of Francis Cardinal Spellman, the Archbishop of New York, and the archdiocese's educational officials.

The initial purpose of the school was to establish a full educational program with a diversity of subject choices, leading to a well-rounded student.

In addition to the college preparatory program, it offered a general course for boys who wanted to finish their education with high school and enter a trade.

Resident at the high school and in semi-retirement was the Catholic scholar, educator, and author Edwin Ryan, D.D.

John O'Keefe, the school's president from 1992 to 2004, was permanently removed from ministry in 2016 because of allegations of sexual abuse of a minor.

[6] O'Keefe's suspension was announced in a December 16, 2015, letter to parishioners from New York's archbishop, Cardinal Timothy Dolan, who called the allegation "credible" .

[16] Stepinac played in the 2016 CHSFL AAA championship game, losing to Cardinal Hayes High School.

[17] Stepinac won the 2017 Catholic High School Athletic Association (CHSAA) New York State Football Championship.

[18][19] Stepinac won the 2018 Catholic High School Athletic Association (CHSAA) New York State Football Championship[20] for the second consecutive year by defeating St. Francis of Buffalo.

[23] On June 11, 1963, the Stepinac Two Mile Relay Team set the National High School record of 7:49.3.