The basis of the dePaul School began with the work of noted psychologist and researcher, Dr. Charles Shedd. Dr. Shedd was Director of the Reading Disabilities Clinic of the University of Alabama School of Medicine, and devoted many years of research into the identification and remediation of students with dyslexia. As a result of his research, he created a curriculum which used specific techniques for teaching reading and spelling to students with dyslexia. Dr. Shedd's work added to the growing body of evidence that children and adults with dyslexia could learn to read, when taught through a multi-sensory, structured linguistics approach.

Sister Anne Rita Mauck, an educator in Louisville, Kentucky, began working with Dr. Shedd in 1965. Building on Dr. Shedd's curriculum, Sister developed an instructional program tailored to meet the academic and organizational needs of children with dyslexia and devoted her entire career to education, and more specifically, to diagnosing and remediating the dyslexic child. She founded the dePaul School in 1970. The dePaul School also guided educators in other states to create schools modeled after the Louisville example.

The Pinellas County dePaul School was established in 1983 by a group of frustrated parents who were unable to find the right learning environment for their dyslexic children. Familiar with the dePaul School in Louisville, they contacted Sister Anne Rita. With training and guidance from Sister and the Louisville school, they established the dePaul School as a non-profit, non-sectarian institution. The sole purpose of dePaul is to assess, remediate and prepare dyslexic students for their future educational placement by providing them with the tools and confidence they need to learn.

In 1983, twenty families began a Tutorial program, meeting initially in the Largo Library. In 1984, a full time school opened for students age 5-14 in Dunedin, Florida. Today, the dePaul School is located in Clearwater and offers a full-time school and a five week Summer Reading Camp.