We evaluated the relative importance of annual rainfall, temperature and their seasonality to tree species distribution in Ghana. We used species presence/absence data from 2505 1-ha plots systematically distributed over Ghana's forests. Logistic regression was used to determine species responses to four climatic variables generated from the Worldclim database. The distribution of 95% of 20 species was significantly associated with annual rainfall, 60% with rainfall seasonality, 45% with isothermality and 40% with temperature seasonality. Annual rainfall explained on average most of the variation (17%, range = 0.5–52%) in species distribution, followed by rainfall seasonality 5% (range = 0.5–27%), isothermality 4% (range = 0.8–24%) and temperature seasonality 1% (range = 0.4–4.5%). Our results suggest that, out of the climatic variables investigated, rainfall is the main factor determining tree species distribution in Ghana; temperature also influences the distribution of a number of species, although it explains much less of the variation. The reduction in annual rainfall that prevailing climate-change scenarios predict for the region will result in a shift in the distribution of most species, whereas the predicted increase in temperature variation is likely to have little effect.