Changes occur to the mandible with dental loss and senescence. However, the influence that these changes have on sex and ancestry estimations remains unclear. The purpose of this study was to investigate the influence of dental loss and senescence on changes in mandibular morphology. The outcome has implications for both forensic anthropology and restorative dentistry. The study sample consisted of 717 mandibles consisting of both male and female South Africans of African (SAA) and European ancestry (SAE). To minimise the effects of variation in dentition amongst sex-ancestry groups, the sample included individuals with a spectrum of tooth loss patterns, namely efficient and inefficient occlusions as well as no occlusions. Dentition was considered efficient when the remaining teeth in occlusion were evenly distributed between the sides. Linear measurements as well as geometric morphometric shape analyses were performed. Shape analyses of the complete mandible were performed on models from digitised landmarks by using a MicroScribe G2. Detailed shape analyses of the ramus and chin area as well as measurements of the cortical thickness at specific sites were executed on images generated by cone beam computed tomography (CBCT). A comprehensive assessment of changes in shape, size and cortical thickness of the mandible with age and dental loss were made. Shape and size differences of the mandible were evaluated for discriminant abilities between sex and ancestry groups. Although most dimensions decreased with tooth loss, the greatest impact was noted in the loss of alveolar bone. The mandibular angle increased minimally in size when a few teeth were lost, but recovered to some extent with further tooth loss. The cortical thicknesses at the mental foramen lingually as well as in the midline in females, were relatively spared with tooth loss. Male individuals of SAA were often the most resilient to tooth loss. In general external linear dimensions were maintained with age despite tooth loss. Conversely, measurements of cortical bone thickness decreased slightly, but could have been influenced by dental loss. The shape of the chin and gonial area was more affected by aging in SAE. The sex and ancestry discriminant ability of the linear dimensions when considered collectively approximated 90%, in general improving further when tooth loss was taken into account. All linear measurements were smaller in females and in general tooth loss accentuated sex differences. SAA exhibited greater dimensions, apart from maximum ramus height, bigonial breadth and cortical thickness at the gonion. The mental tubercles were more prominent than the pogonion in SAE (square chin) and vice versa in individuals of SAA (pointed chin). The gonial area in individuals of African ancestry was broad and more convex and the gonial eversion more prominent with a more upright ramus. Discriminant qualities of the gonial shape for sex in individuals of African ancestry reached 90% within dentition groups. Ramus flexure and chin shape were not found to be useful in sex estimation. In conclusion, this research elucidated the effects of tooth loss and senescence on the morphology of the mandible for the forensic anthropological setting.