Drought negatively affects cotton growth and yield, whereas excessive irrigation can limit yield through excessive vegetative growth and poor fruit retention. Mepiquat chloride (MC) application limits plant height, improves fruit retention and hastens maturity in responsive cultivars. Thus, the objective of this study was to address the effects of cultivar, irrigation, and MC strategy on cotton growth, maturity, yield, and fiber quality. Therefore, a field study was carried out using three cultivars, three different irrigation treatments, and three different MC treatments during the 2020 and 2021 growing seasons. In both years there was an interaction between irrigation and MC management for plant height. In 2020, MC treatments hastened cutout by two to three weeks in irrigated plots but did not affect cutout date in dryland plots. 2020 and 2021 differed substantially in rainfall (347 mm and 735 mm, respectively from planting to harvest). 2020 was a dry year in which yield responded positively to irrigation and 2021 was a wet year in which yield responded negatively to irrigation. There was no effect of MC treatments or interaction between MC and any other effect on lint yield. Fiber length was reduced, whereas strength and micronaire were increased by drought stress in 2020. Increased fiber length, strength, uniformity, and micronaire were observed by MC application in both years. Therefore, we can conclude that aggressive MC management reduces vegetative growth, promotes earlier physiological maturity under well-watered conditions, and affects fiber quality, but does not necessarily interact with irrigation management to affect lint yield. • Growth and maturity responses to mepiquat chloride depend on water availability. • Mepiquat chloride hastens maturity under water replete conditions, but not dryland. • Occasionally, fiber quality was positively impacted by mepiquat chloride application. • Mepiquat chloride did not alter cotton yield response to water excess or drought.