Pearl millet [Pennisetum glaucum (L.) R. Br.] is an important food-security crop to smallholder farmers in West Africa (WA). Breeding for high yield and stability is a major challenge in the harsh environments of WA but could be tackled by hybrid breeding. Knowledge of combining ability patterns and quantitative-genetic parameters is required for an efficient development of hybrid varieties. Hence, our objectives were to estimate the combining ability of seven genetically diverse Sahelian pearl millet populations from Senegal, Mali, Benin, Burkina Faso, Niger, Sudan and Nigeria and the heterosis and stability of their 42 diallel-derived population hybrids to inform pearl millet hybrid breeding. The genotypes were evaluated in six environments in WA in 2007. Grain yield (GY) exhibited an average panmictic mid-parent heterosis (PMPH) of 24%, ranging from -1.51% to 64.69%. General combining ability (GCA) was significant across test environments as reflected by high heritability estimates and high GCA:SCA variance ratios. Thus, early selection for parental per se performance would be rewarding. The parental population from Sudan (IP8679) had strongly negative GCA for GY. Its lack of adaptation contributed to the predominance of additive effects in the present germplasm set. Parental populations PE02987 (Senegal), PE05344 (Mali) and ICMV IS 92222 (Niger) showed large positive GCA for GY. Their offspring, especially PE02987 × PE05344 and Kapelga × ICMV IS 92222, exhibited a high and stable GY across all test environments. Tapping the regional pearl millet genetic diversity seems therefore beneficial for hybrid breeding to increase pearl millet productivity in WA.