An investigation of bone microstructure of nonmammalian therapsids has revealed distinctive signals pertaining to their ontogenetic growth and biology. Until now, histological studies of the nonmammaliaform cynodonts have focused only on postcranial material. Through the examination of micro-computed tomography (micro-CT) scans and serial thin sections, the current study provides a novel perspective on the structure and growth of the mandible of Tritylodon, a derived herbivorous cynodont from southern Africa. By tracking histological features across the serial thin sections, trends in relocation and modelling are documented for the growing Tritylodon mandible. For example, during growth, localized changes in the cross-sectional shape of the mandible occurred. Localized deposits of new lamellar and fibrolamellar bone on the lateral edge indicate widening of the mandible during different episodes of growth. The presence of radial channels indicates the deepening of the mandible at its anterior and posterior ends. The relocation of the paired mental foramina suggests that the mandibular body lengthened mainly in the posterior direction. The medial movement of a posterior postcanine tooth during growth and eruption is recorded in the histology. This histological assessment also documents the presence of Sharpey’s fibres in the cellular cementum of the first incisor, providing novel and unequivocal evidence that it was attached to the Tritylodon jaw by a periodontal ligament. This is the first comprehensive study that uses histological analysis to document the growth dynamics of the mandible of a nonmammalian therapsid, thus providing a unique perspective of localized mandibular growth in a fossil animal.