Large earthquakes away from plate boundaries pose a significant threat to human lives and infrastructure, but such events typically occur on previously unknown faults. Most cases of intra-plate seismicity result from compression related to far-field plate boundary stresses. The April 2017 Mw 6.5 earthquake in central Botswana, and subsequent events, occurred in a region with no previously known large earthquakes, occurred away from major present day tectonic activity, and accommodate extension rather than compression. Here, we present results from an integrated geophysical study that suggests the recent earthquakes may be a sign of future activity, controlled by the collocation of a weak upper mantle and weak crustal structure, between otherwise strong Precambrian blocks. Magnetotelluric data highlights Proterozoic continent accretion structure within the region, and shows that recent extension and seismicity occurred along ancient thrust faults within the crust. Our seismic velocity and resistivity models suggest a weak zone in the uppermost mantle, that does not persist to greater depths, and is therefore unlikely to represent mantle upwelling. The Botswana events may therefore be indicative of top-down extension as a response to large scale extensional forces.