Considering the high importance of maize as a subsistence crop and the need for optimal use of water resources in semi-arid regions, this study aimed to evaluate the agronomic potential, heterosis, and heterobeltiosis within different genetic categories of maize hybrids grown in a semi-arid region in Sergipe, Brazil, under rainfed and wastewater irrigation systems. Ten maize genotypes, their 45 hybrid combinations, and five commercial genotypes as controls were evaluated based on plant height, ear height, and grain yield. Positive heterosis and heterobeltiosis were found under both growing environments for hybrids H1, H13, H16, H32, H35, H5, H8, and H9. Genotypes P2, P3, and P9 were identified as potential parents for the development of new hybrid maize varieties for growing in the semi-arid region of Sergipe. Better agronomic performance was found for the wastewater irrigation system, indicating an excellent strategy for maize production under semi-arid conditions. The hybrids formed by the combination of variety × intervarietal hybrid [F1 (P1 × P2), F1 (P1 × P5)], variety × single hybrid [F1 (P2 × P6), F1 (P2 × P9), F1 (P5 × P7), and F1 (P5 × P10)], intervarietal hybrid × single hybrid [F1 (P1 × P6) and F1 (P1 × P9)], and double hybrid [F1 (P1 × P10)] indicate promising hybrid candidates for maize crops in semi-arid regions.