The formation of the largest and most ancient lunar impact basin, South Pole–Aitken (SPA), was a defining event in the Moon’s evolution. Using numerical simulations, we show that widespread mantle heating from the SPA impact can catalyze the formation of the long-lived nearside-farside lunar asymmetry in incompatible elements and surface volcanic deposits, which has remained unexplained since its discovery in the Apollo era. The impact-induced heat drives hemisphere-scale mantle convection, which would sequester Th- and Ti-rich lunar magma ocean cumulates in the nearside hemisphere within a few hundred million years if they remain immediately beneath the lunar crust at the time of the SPA impact. A warm initial upper mantle facilitates generation of a pronounced compositional asymmetry consistent with the observed lunar asymmetry.