Regionalisation is considered to be a hallmark of the Middle Stone Age (MSA) compared to the Early Stone Age. Yet what drove diversification around a shared technological substrate that persisted across Africa for hundreds of thousands of years remains debated. Non-mutually exclusive hypotheses include region-specific styles in manufacture, social signalling, cultural drift between geographically isolated populations,, and diverse environmental adaptations, as well as the impacts of unequal research histories and intensities. We explore the potential ecological bases of behavioural diversity during the MSA between two well-studied and diverse areas: eastern and northwestern Africa. We utilise a set of standardised bioclimatic simulations, as well as a time series decomposition algorithm, to determine the nature and extent of regional differences in terms of environmental productivity, seasonality and predictability at MSA sites through time. Our results highlight that, compared to human occupations of eastern Africa, northwestern African MSA occupations are associated with colder, drier and less productive environments, albeit wetter, colder, and more productive compared to surrounding areas, with higher temperature seasonality and more predictable climates across millennia. We then theoretically consider the implications of our results for technological diversification between these two regions during the Middle to Late Pleistocene, such as for the investment in specific risk mitigation strategies for dealing with seasonally mobile resources in northern localities, and the diversification of flexible MSA toolkits in tropical eastern Africa.