Background <p>Drought stress severely limits maize production in Northwest China. Although melatonin is known to enhance plant stress tolerance, its specific mechanisms in maize have not been fully elucidated. To address this, we investigated whether melatonin improves drought tolerance using two contrasting maize genotypes: drought–tolerant (SD–609) and drought–sensitive (SD–902). A experiment was conducted under drought stress with and without melatonin application, in which we have analyzed photosynthetic parameters, antioxidant enzyme activities, oxidative stress markers, key components of CO₂ assimilation, and dry matter accumulation.</p> Results <p>Under drought stress, melatonin application significantly enhanced photosynthetic performance by improving dark reactions (upregulation of CO₂ assimilation enzymes and genes). It concurrently activated the antioxidant system (SOD, CAT, POD, and the AsA–GSH cycle), leading to a marked reduction in H₂O₂ and MDA levels. These synergistic improvements resulted in a significant increase in dry matter production. The drought–tolerant genotype (SD = 609) exhibited a more pronounced response to melatonin across these parameters than the sensitive genotype (SD = 902).</p> Conclusions <p>This study demonstrated the co–activation of key photosynthetic and antioxidant pathways. The stronger effect in the drought–tolerant genotype suggests an interaction with inherent genetic capacity. These findings provide a crucial theoretical basis for the application of melatonin as a potential agrochemical to enhance crop resilience in water–limited environments.</p>