Aim To investigate whether morphological variation in a continental radiation of lizards (Chamaeleonidae) was driven by ecological opportunity. Location KwaZulu-Natal, South Africa. Methods Chameleons from all morphotypes were genotyped (n=279) using 10 microsatellite and one mitochondrial marker (n=130). Genetic spatial structure was examined in a Bayesian framework and compared to ecomorphological forms, to identify distinct chameleon groups using a total evidence approach. Ecological niche modelling projected back to the Last Glacial Maximum and the Last Interglacial was used to make inferences regarding the processes that may have facilitated diversification through ecological opportunity. Results For the three inland groups, genetic and morphological evidence were in agreement suggesting these are candidate species. However, there was discordance in evidence for populations from coastal regions, although the different time-scales of the data allow us to make some inferences regarding this disparity. The microsatellite data suggest at least three independent origins of coastal chameleons, although all three clusters show the same ecomorph, which indicates convergence of phenotype in a similar environment. The species distribution models revealed high niche stability among inland groups, suggesting the presence of refugia for these chameleons; whereas the coastal niche is more dynamic and likely resulted in recent origins of these groups. Main Conclusions A dynamic climatic niche and corresponding vegetation shifts are likely to have shaped contrasting ecomorphological and genetic patterns within this continental radiation by creating ecological opportunity for the coastal chamleons. In contrast, inland groups are in climatically stable regions, and show concordance between lines of evidence, suggesting that niche stability has allowed for these chameleons to diverge genetically and phenotypically.