Bishop Mora Salesian High School was built during the tenure of Cardinal James Francis McIntyre and opened in 1958 as an archdiocesan school staffed by the Salesians of Don Bosco.  The school offered four distinct academic programs: college preparatory, business, general education, and shop.  Throughout the 1960's and early 1970's, Salesian was well known for its strong shop programs in printing, drafting, woodworking, and electronics.  During these years, the student body reflected the ethnic diversity of the neighborhood and was comprised of Latinos, African-Americans, Japanese-Americans, and Caucasians.  As the East Los Angeles area and surrounding communities became increasingly Latino, so did the ethnic make-up of the school.  Today, the student body is 96% Latino. 

The Chicano movement of the early 1970's impacted the school's identity and curricular program.  Salesian responded to the community's emphasis on the importance of one's heritage and culture and call for greater academic opportunities for the Latino community.  The administration discontinued the shop and business programs and redirected resources into the college preparatory offerings.

In 1988, the Salesians of Don Bosco responded to their declining number of religious in the Western Province by withdrawing from the administration of Salesian High School.  During the following three years, the first two lay principals led the school. 

In 1992, the Provincial Chapter of the Salesian Society reaffirmed its support of Salesian High School and informed the Archdiocese of Los Angeles of its desire  to reestablish an official relationship with the school.  The model agreed to by both parties affirms Salesian High School as a Salesian work that participates in the educational workshops, pastoral retreats, and scholarship programs of the Salesians of Don Bosco.  By agreement with the Archdiocese, the principal will be a lay person familiar with the Salesian Preventive System of Education.  There will be a professed Salesian presence at the school and the spirit of St. John Bosco will continue at Salesian High School.

During the mid to late 1990's, Salesian experienced an increase in enrollment and an improvement in its financial picture.  The faculty designed a diversified curriculum aimed at offering young men of different needs and talents the opportunity to attend a Catholic secondary school.  A new Advisory Board assisted the school administration in establishing a development program and drafting proposals for an overhaul of the school's physical plant.  In 1998, the John and Dorothy Shea Foundation announced a $7 million grant to partially finance the construction of new academic, athletic, and multi-purpose facilities on the campus.  Construction of these new facilities was completed in 2002 with Cardinal Mahoney presiding at the dedication.  The statue of Don Bosco was placed once again in its place of honor, facing the entrance of the school building.  Bishop Zavala lead the prayers for the rededication of the statue, urging all to be active ministers of the Word of God.