The effect of melatonin application on enhancing plant stress tolerance is already known, but the specifics of its performance and its underlying mechanism are still poorly understood. The influences of foliar-sprayed melatonin (100 μmol/L) on maize (Zea mays L.) seedlings growth during drought stress were investigated in this study. The growth of seedlings was not affected by melatonin application under normal conditions. After 8 days of drought stress, growth was significantly inhibited, but this inhibition was alleviated by foliar-spraying with melatonin. After rehydration, melatonin-treated plants recovered more quickly than untreated plants. Further investigation showed that, under drought condition, melatonin-treated plants showed higher photosynthetic rates, stomatal conductances and transpiration rates than those untreated plants. Compared with untreated plants, the melatonin-treated plants exhibited low osmotic potential under drought stress, which contributed to the maintenance of high turgor potential and relative water content. Drought stress induced the accumulation of hydrogen peroxide and malondialdehyde, but the accumulation was decreased by melatonin application. Also, both enzymatic and nonenzymatic antioxidant activity were enhanced by melatonin application under drought stress. These results imply that the effects of melatonin on enhancing drought tolerance can be ascribed to the alleviation of drought-induced photosynthetic inhibition, improvement in plant water status, and mitigation of drought-induced oxidative damage. The results suggest that melatonin could be considered as a potential plant growth regulator for the improvement of crop drought tolerance in crop production.