Increasing water-use efficiency by optimizing planting density and irrigation regimes in maize is crucial for food security under limited water resources. In this study, six plant densities (6.0, 7.5, 9.0, 10.5, 12.0, and 13.5 × 104 plants ha−1) and three irrigation amounts (300, 450, and 600 mm) were assessed to analyze the effects of planting density and irrigation amount on the yield and yield components. We also explored the combination of maize production capacity and maximizing economic returns in a planting region. The results demonstrated that as planting density increased, grain yield first increased and then decreased. The optimum planting density was 9 × 104 plants ha−1 when the irrigation amount was 300 mm, and 10.5 × 104 plants ha−1 under both 450 mm and 600 mm irrigation amounts. The relationship between planting density, irrigation amount, planting area, production capacity, and economic return showed that a current production capacity with 6.75 × 104 plants ha−1, 600 mm, and 1.066 million ha, could be achieved with 10.5 × 104 plants ha−1, 344 mm, and 1.1 million ha. The water-use efficiency of irrigation was increased by 74%. Current returns could be achieved with 10.5 × 104 plants ha−1, 405 mm, and 1.1 million ha, or by 9.0 × 104 plants ha−1, 449 mm, and 1.1 million ha. These observations demonstrated that appropriately increasing the planting area and reducing the irrigation amount per hectare under an optimal planting density could achieve a greater economic return and water-use efficiency than either increasing the planting density or reducing the irrigation volume alone in North Xinjiang. We concluded that concurrent optimization of the maize planting density, irrigation amount and plant area will not only meet the demand of food security but also achieve a rational use of water resources and farmland.