The continued improvement in the yield of cowpea for the semi-arid regions where it is a dominant crop will record rapid progress if the genetic basis for yield under different moisture regimes is better understood. This study investigated the genetic combining abilities and heterosis for grain yield, yield components, flowering and biomass production among diallel hybrids derived from nine cowpea genotypes. Results showed that moisture stress significantly reduced grain yield, biomass production, and number of pods per plant. Only for grain yield was a significant interaction observed for moisture regimes. Genetic control for grain size, number of seeds per pod and days to flowering was dominated by additive genetic effects. For grain yield, both additive and non-additive genetic effects were dominant. The genetic control of yield under the two soil moisture conditions indicated that grain yield improvement will be more challenging for drought prone regions. Nonetheless, careful selection of genotypes that have complementary but different alleles for yield under different soil moisture conditions might permit yield improvement through recurrent selection. This study has identified parental lines, developed populations, and provided a breeding strategy for developing cowpea cultivars with higher grain yield for Guinea and Sudan savannah regions of West Africa.