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 a more systematic exploitation of hybrid vigor and heterosis in breeding of both open-pollinated varieties (OPVs) and different types of hybrids. Knowledge of combining ability patterns and quantitative-genetic parameters is required for an efficient development of hybrid vigor and heterosis in breeding programs. Hence, our objectives were to complement other existing studies and estimate the combining ability of seven unique, highly 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 (or hybrid populations) to inform pearl millet OPV and hybrid breeding. The materials were evaluated in six environments in WA in 2007. Grain yield (GY) exhibited an average panmictic mid-parent heterosis 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 and preselecting the crossing parents seem beneficial for OPV and hybrid breeding to increase pearl millet productivity in WA.