This study builds on the fundamentals of the new economic geography and the skill-biased technological change argument, to empirically investigate whether increasing income/earning inequality enhances total factor productivity in South Africa. In so doing, panel data of district-municipalities and spatial econometric techniques are used for the period between 1995 and 2015, to gain a better understanding of the role of location and distance in the effects of income inequality on total factor productivity. The results from the analysis and empirical estimations indicate that: (1) there is strong support for the existence of positive spatial interactions in the effects of income inequality on total factor productivity; (2) the estimated direct effect of income inequality on TFP in local district-municipalities is negative and statistically significant, while the indirect effect is positive and statistically significant as well. These findings suggest that district-municipalities with moderate levels of inequality and high economic opportunities, attract more businesses, investments and important stocks of skilled labour from district-municipalities with high inequality. Furthermore, the finding of negative effects supports previous research suggesting that high levels of inequality set the stage for the adoption of distortionary policies which adversely influence the investment climate and produce political instability, thereby stifling the level of productivity and growth.