St. Louis Catholic School began as a simple seven-room schoolhouse which first opened its doors on September 2, 1947. At that time it was part of the Combined Roman Catholic Separate Schools Board of the Township of Etobicoke. In the first year, there were 71 students from grades 1 to 8, with two teachers: Sister Mary Assumpta was the first principal of St. Louis. It was she who established the school motto of “faith, friends and fulfillment”.

In the years that followed, the school continued to grow. In 1962, the school gained an addition of five classrooms and a library. In 1967, St. Louis joined the Metropolitan Separate School Board (now Toronto Catholic District School Board) family. In 1968, a gymnasium and three more classrooms were added. In 1990, the original schoolhouse was torn down. The addition and renovations which make up the present building were completed in 1992.

In April 26, 2016, it was announced that Ontario was investing $12 million into Etobicoke's Catholic community with a state-of-the-art new school & liscenced child care centre. 

The new facility will accommodate 500 Catholic students from Junior Kindergarten to Grade 8. The new school will bring together students currently attending St. Leo Catholic School & St. Louis Catholic School. Once built, the new facility will provide a modern learning environment, enhanced programming and better support for student achievement and well-being.