The idea for the high school began in the mid-1940s and was the "vision of Father J. Nuevo, C.M.F., Mission San Gabriel pastor.

With the need for a high school and the support of his parishioners, Father Nuevo had collected a sizable $245,000 toward the realization of the project."

"only enjoyed a pastorate for a few months, as his success in dealing with the complexities of the new school building project resulted in his election as General Treasurer of the Claretian Fathers."

San Gabriel Mission High School opened in September 1949 as a co-institutional school, which meant that boys and girls were taught separately, the boys' section administered by the Claretian Fathers and the girls' section administered by the Dominican Sisters of Mission San Jose.

The freshmen class had 119 girls and boys, temporarily quartered in All Souls Grammar School in nearby Alhambra.

Dedication ceremonies took place on January 14, 1951, with Most Reverend J. Francis McIntyre, Archbishop of Los Angeles, officiating.

The boys were able to join football, basketball, track, soccer, golf, bowling and tennis teams.

In 2007, Mission TV went live on the internet and in 2009, the Cultural Room opened, where language clubs host meetings.

Notable alumni include: Father Ralph Berg, CMF '53, returned to Mission as pastor in June 1978, serving the parish for three years in this capacity.

Peter Mullin '58, businessman and owner of the Mullin Automotive Museum; Dr. Katherine Medvetz Poehlmann '60, author; Father Frank Ferrante, CMF '62, served as Provincial for the Claretian order; Katherine Burns Sartori ‘63, author; renowned soprano Alba Quezada ‘71 and mezzo-soprano, Suzanna Guzman ‘73; and Carol Najera Edwards '78, Deputy District Attorney.

Student commute from various cities from the San Gabriel Valley and Greater Los Angeles Region.