Due to varying crop responses to water stress at different growth stages, scheduling irrigation is a challenge for farmers, especially when water availability varies on a monthly, seasonal and yearly basis. The objective of this study was to optimize irrigation between the vegetative (V) and reproductive (R) phases of maize under different available water levels in Colorado. Long-term (1992–2013) scenarios simulated with the calibrated Root Zone Water Quality Model were designed to meet 40%–100% of crop evapotranspiration (ET) requirements at V and R phases, subject to seasonal water availabilities (300, 400, 500 mm, and no water limit), with and without monthly limits (total of 112 scenarios). The most suitable irrigation between V and R phases of maize was identified as 60/100, 80/100, and 100/100 of crop ET requirement for the 300, 400, 500 mm water available, respectively, based on the simulations from 1992 to 2013. When a monthly water limit was imposed, the corresponding suitable irrigation targets between V and R stages were 60/100, 100/100, and 100/100 of crop ET requirement for the above three seasonal water availabilities, respectively. Irrigation targets for producing higher crop yield with reduced risk of poor yield were discussed for projected five-year water availabilities.