Waterlogging represents a serious abiotic stress for plants that retards crop growth and reduces production. Therefore, exploration of effective ways to alleviate the impacts of waterlogging has important theoretical and practical applications. This study investigated the responses of seedlings of two sorghum cultivars with different waterlogging tolerances to exogenous foliar treatment with melatonin (MT) and nitrogen (N) under waterlogged conditions. The chlorophyll fluorescence, photosynthetic capabilities, and antioxidant enzyme activities of these seedlings were measured after treatments with waterlogging and either exogenous application of MT, N, or both. The results showed that waterlogging severely limited sorghum growth and reduced dry matter accumulation in both cultivars. However, the negative effects of waterlogging were mitigated by spaying MT and N on leaves, especially of the waterlogging sensitive cultivar. Notably, exogenous foliar spraying of MT and N enhanced the chlorophyll content and improved the maximal quantum yield of photosystem II photochemistry (Fv/Fm), resulting in higher rates of photosynthesis. In addition, exogenous spraying of MT and N markedly decreased the malondialdehyde (MDA) content by upregulating antioxidant enzyme activities. The results also show that the combined effects of MT and N were better than the application of either alone and that exogenous foliar spraying of MT and N significantly increased the soluble protein content of leaves of sorghum. Overall, these results indicate the beneficial roles of MT and N in alleviating waterlogging stress in sorghum and show that their application may represent a strategy to mitigate waterlogging stress during agricultural production.