Cowpea is a high-protein legume. Water stress is the most significant obstacle that hinders agriculture development in regions with limited water resources. Drought stress affects cowpea production, i.e., growth, yield and quality. An experiment was conducted to evaluate some cowpea accessions for drought tolerance at reproductive stage and studying the physiological, molecular and anatomical basis of tolerance. Six accessions were selected from a previous investigation to study the nature of drought tolerance at reproductive stage. Accessions TVU-14997, TVU-15304 and TVU-15306 exhibited high drought tolerance based on their high levels of each of antioxidant capacity, total phenols, catalase, peroxidase and abscisic acid during reproductive stage. The molecular study using specific primers confirmed the agronomical findings. The identification of potential genetic markers associated with drought tolerance in this study is a promising avenue for future research. The development of molecular markers for drought tolerance can facilitate marker-assisted selection in breeding programs, accelerating the development of drought-tolerant cowpea varieties. Regarding anatomical structure, under drought condition, accession TVU-15306 had the highest value for thickness of the midvein, spongy tissue, dimension of vascular bundle and mean vessels diameter. Water stress was found to negatively affect growth of studied cowpea accessions. Results showed that accessions TVU-14997, TVU-15304 and TVU-15306 were drought tolerant as evidenced by high levels of each of antioxidant capacity, total phenols, catalase, peroxidase and abscisic acid. They can be used as sources of tolerance to drought stress in breeding programs.