Pascoe Vale Girls School opened in 1956 with an enrolment of 115 girls. Until the completion of the first section of buildings, classes were conducted in the Holy Trinity Parish Hall in Pleasant Street, and the Central Progress Association Hall in Park Street. Miss K.D Meldrum was appointed as the first Head Mistress. Classes were first conducted in the buildings on the permanent site in Lake Avenue in February 1957. By this time, the school enrolment had risen to 500 students. The second and third sections of the main school were completed and occupied by 1962. A foundation ceremony was held, at which the Director of Education, Mr. A. McDonell, unveiled a plaque to commemorate the completion of the main building.

In 1963, Miss E.D. Daniel was appointed Head Mistress. Miss Daniel strove to raise the status of girls and women and to forge attitudes for girls to reach their academic potential and seek professional and leadership roles in the community.

Pascoe Vale Girls lost its "Girls Domestic School" stigma and became a High School in 1966. In 1968, the E.D Daniel Assembly Hall was officially opened, and enrolments continued to increase, despite the fact that there was no sixth form and the most talented students had to transfer to other schools to continue their final year of education.

In 1975 Mr E. De Motte was appointed Principal.

A Commonwealth Science block was added to the site and the George O'Brien Oval was named after the School Council President who had served the school for eighteen years. The student population grew to 825 and the E.De Motte Library was built.

Miss Helen Jackson was appointed principal in 1987.  In 1991 Pascoe Vale Girls School became a Secondary College.

In 2002 the school was re-named Pascoe Vale Girls College.  

In 2009, the school received $6.3 million for renovations and new buildings, which were completed in 2011.

The College celebrated it's 60th anniversary in 2016.

The current Principal Ms Kay Peddle was appointed in 2015.