Historical Ramona Convent Secondary School's first building was dedicated at Ramona Acres, on January 29, 1890 on the expansive property that was later called Shorb, and is now part of the City of Alhambra. The Sisters of the Holy Names of Jesus and Mary came from Oakland at the request of several prominent San Gabriel Valley families interested in the Catholic education of their daughters. The James de Barth Shorb Family donated fifteen of the thirty-one and a half acres of the original property. The first building to be built was a four-story red brick building on the knoll that dominated the Convent grounds. The dedication ceremony was presided over by the Right Reverend Bishop Mora of Los Angeles on January 29, 1890. The first commencement exercises were held on June 23, 1891. The groundbreaking ceremony for the major part of the school, took place April 18, 1910. Three years later the new chapel was dedicated by the Right Reverend Bishop Conaty of Los Angeles. In the years that followed, several additions were made, including the boarding school housing, gymnasium, Junior Living Room, swimming pool, English Wing, Science Building, Sisters' Residence and the stables. In 1939, 3 acres (12,000 m2) were sold to the State of California for the San Bernardino, Interstate 10 Freeway.

In 1967 a Master building plan was developed and implemented, first adding the library with computer and language labs in 1967. Approximately four acres of the southwestern section of Ramona's property were sold In 1979 in order to help fund further implementation of the Master Plan. Additions to the Plan included the 16-classroom Dufresne Building and the multi-purpose gymnasium. Those buildings were dedicated in February 1981. Because of extensive damage caused by the October 1, 1987, Whittier Narrows earthquake, the main buildings built between 1889-1912 were soon demolished. A building to house administrative offices, kitchen and dining facilities, and a chapel was dedicated on November 12, 1989, the beginning of Ramona's second century of excellence. Ramona received Blue Ribbon School of Excellence status from the U.S.
Department of Education in 1983 and again in 1998.