The spatial coupling of population and economy is an important indicator that reflects regional differences and measures the coordination degree of industrial layouts and environments. To explore the spatial coupling of population and economic densities and the effect of topography in Anhui Province at a grid scale, a land-use impact model was used to spatialize socio-economic indicators in Anhui Province using 2020 county-level data. Geographical concentration and coupling index were used to quantify the spatial relationship between population and economic densities. Then the effects of topography were assessed. The results show the following: (1) the accuracy of the regression models for the individual counties is generally better than that of the models for the whole region. The population and economic densities predicted by the proposed model reflect actual conditions. (2) Topography has a stronger effect on population density and primary industry density than on secondary and tertiary industry density. Slope has the strongest effect on population and economic densities, followed by topographic relief and elevation. (3) A spatial correlation exists between topographic factors and population and economic densities. Although the spatial relationship between population and economic densities is predominantly of the balanced development type in regions with complex topography, population and economic densities are significantly lower in regions with complex rather than flat topography. In addition, economic development in the northern Anhui region, a flat region, lags behind population aggregation. Efforts should be made to improve the economic level of the southern and northern Anhui regions and the Dabie Mountain region in western Anhui.