In the spring of 1960, an eight-room elementary school was built on the grounds of St. Mary's Parish.  The Pastor, Fr. Martin Hiss, officially opened the school in the fall of 1960 with 42 first grade students and 30 second grade students.  A parishioner, Mrs. Rae Henry, became Principal: Mrs. Margaret Wilhelm took charge of first grade and Mrs. Chamblin taught second grade.  Registration for the 1961 -1962 school year more than doubled with the addition of the third, fourth, and fifth grades.  At the invitation of the Pastor, three Immaculate Heart of Mary Sisters, Sr. Martin de Porres, Sr. Mary Edwardine, and Sr. Mary Noemi assumed the roles and responsibilities of the administration, first and second grade teachers.  The first graduation from St. Mary's took place in 1965 with 33 students.  The Sisters of the Immaculate Heart of Mary continued their dedicated service to the school until June of 1968, when their community withdrew from the parish.

In 1968, His Eminence James Cardinal McIntryre of Los Angeles extended an invitation to the Salesian Sisters to assume the administration, and partial staffing for the school.  On September 10, 1968, 272 students began their first day of school.  Palmdale had a population of 23,000.  In the 1970s, unstable employment in the area caused the general population, as well as the school population, to be extremely mobile.

The 1980s, 90s, and early 2000s saw a more stable school population as families commuted to work in the San Fernando Valley.  Saint Mary's rapidly grew to a parish with the largest geographical area in the Archdiocese.  The parish includes three missions, Acton, Littlerock, and Lake Los Angeles.  The population of Palmdale has now grown to over 160,000.  The school staff has expanded from the original three parishioners to include 31 educators and support staff producing an Early TK-8 school.  A lay principal assumed the administration of the school.

St. Mary School is accredited by the Western Catholic Educational Association and the Western Association of Schools and Colleges.