In 1968, the Foundation held a capital campaign capped by a donation of land from philanthropist Paul D. Perkins, whom he made in honor of his late daughter, Mary Bird.

In 1971, the Mary Bird Perkins Radiation Treatment Center opened its doors in Baton Rouge.

After 14 years of operation, in 1985, Mary Bird Perkins relocated to its present site on Essen Lane and installed the first linear accelerator in the state.

In 2018, Mary Bird Perkins – Our Lady of the Lake Cancer Center and Woman's Hospital opened the Breast & GYN Cancer Pavilion and partnered with Lane Regional Medical Center in Zachary.

Additionally, the Cancer Center partners with LSU Health Baton Rouge North Clinic.