Oral Pathology positioned itself as an integral part of the Dental Faculty at its establishment in 1951. At that time, the Faculty consisted of four departments, namely Prosthetics & Dental Technology, Operative Dentistry, Conservative Dentistry & Orthodontics and Dental Anatomy, Physiology, Pathology & Histopathology. The Faculty started with 66 first-year students, 33 second-year students, 22 third-year students and 18 fourth-year students.

From 1951 until June 1952, Prof Julius Staz, Head of the Department of Oral Science at the University of the Witwatersrand, was a part-time lecturer in the Department. He lectured a course titled Pathology and Histopathology of the Teeth and Mouth.

Prof Chris de Jager was appointed as Professor and Head of this Department in 1952. Prof De Jager also became Dean of the Faculty in 1956 after the death of Prof Phil Joubert. He held both these positions until his retirement in 1966.

Prof L M Jonck was appointed Professor and Head of the Department on 1 July 1967. Prof Jonck was one of the first dental students to qualify at the University of Pretoria. He obtained his BChD degree in 1952 and in 1965 his MChD degree in Maxillofacial and Oral Surgery. In 1980 Prof Jonck retired as Head of the Department after 25 years of service to the University of Pretoria, and became Director of the Institute of Stomatology and Bone Biology on a full-time basis.

On 1 April 1981 Prof A J Ligthelm was promoted to Professor and Head of the Department. He held this position until his appointment as Dean of the Faculty Dentistry in March 1996. Prof Willie van Heerden is the current Head of the Department.

The Department has undergone a number of name changes during its history. It has variously been known as the Department of Dental Anatomy, Dental Physiology, Pathology and Histopathology, the Department of Pathology and Histopathology of the Oral Cavity and the Department of Oral Pathology and Oral Medicine. Most recently the Department of Oral Pathology and Oral Biology, when Oral Medicine was incorporated into the Department of Periodontics. In 2009 the Department of Radiography ceased to exist as it was absorbed into the Department of Oral Pathology and Oral Biology as Diagnostic Imaging, in keeping with modern imaging trends.