The Cape Floristic Region (CFR) is well-known for its floral diversity, yet also contains a rich herpetofauna with >180 species, 28% of which are endemic. Recent studies conducted on CFR lizards indicated that phylogeographic patterns show some congruency, and that the western CFR shows higher overall diversity in the form of population and/or clade turnover. Here, we combine mitochondrial sequence data from two published (Bradypodion spp. and Agama atra) and one new dataset (Pedioplanis burchelli) to investigate whether geographic patterns of genetic diversity could be influenced by predicted climatic changes. We utilised Bayesian methodology and spatial genetic landscapes to establish broad-scale patterns and show that the western CFR is a contact zone for several clades in all three taxa, supporting the hypothesis of phylogeographic congruence. Current levels of gene flow are virtually zero between the western and eastern CFR. In the east, gene flow between populations is negligible at present but was probably stronger in the past given the present lack of strong genetic structure. Bioclimatic modelling predicted that climatically suitable areas within the CFR will decline for Bradypodion spp. and P. burchelli, with areas high in clade turnover loosing more climatically suitable areas than areas with low clade turnover. The models also predict that loss of climatic suitability may result in highly fragmented and patchy distributions, resulting in a greater loss of connectivity. In contrast, A. atra does not show significant climatic suitability losses overall, although it may experience localised losses (and gains). This species is not predicted to loose suitability in areas of high clade turnover. Thus, the incorporation of genetic data into climatic models has extended our knowledge on the vulnerability of these species given the predicted threat of landscape change.