On 25 February 1917, the parish community of Clifton, led by Father Mark Cosgrove, welcomed four Good Samaritan Sisters to establish a Catholic primary school. The original Clifton Church was moved to Tooth Street behind the convent and renovated to become the first Convent School. 
As the years passed, Monsignor Michael McKenna, then Parish Priest, saw the necessity for a new and larger school. The present two-story block was built on the ground adjoining the convent in Meara Place and was named St Francis de Sales School. St Francis de Sales Catholic Primary School was blessed and opened by Bishop Brennan on the 5th August 1962. In this new and large building, the educational traditions, begun by the Good Samaritan Sisters some forty-five years earlier, continued to be provided for the children of the Clifton Parish. 
Eight years later, the Headington Hill State School was purchased and brought to the grounds to become the Infant School. This building currently holds the staff room. 
In 1979 the Good Samaritan Sisters left the parish and since then the school has been operated by lay staff, supported by the Toowoomba Catholic Education Office, now known as the Toowoomba Catholic Schools Office. 
In the year 2000 the school undertook a major refurbishment program. All classrooms were repainted and carpet laid. A separate room was built for students to receive additional assistance with the learning support teacher. Cabling was laid enabling computers to be networked and allowing for all students to have access to the Internet. The administrative area of the school was modified as well. 

In 2010 a new administration building was built at the front of the school.

St Francis De Sales School continues to serve the families of the Clifton area in ensuring all students experience academic success and come to know the person and teachings of Jesus.