Water scarcity threatens the sustainability of irrigated cotton production in many regions around the world. Consequently, there is a critical need to identify and test strategies that optimize water use for cotton production. This 4-yr study evaluated the effects of three irrigation treatments (full irrigation [FI], reduced irrigation [RI] at 75% of FI, and no irrigation [NI]) on cotton yield, fiber quality, and irrigation water use efficiency (IWUE) at a field that relies on groundwater for irrigation in west-central Oklahoma. Compared with FI, lint and seed yields did not change significantly under RI. The reductions in lint and seed yields were significant at 64 and 65% under NI, respectively, compared with FI. No significant differences in fiber quality were observed among the irrigation treatments. In addition, reducing irrigation application improved the IWUE of lint and seed by 9 and 8%, respectively. Based on these findings, reducing groundwater extraction by 25% appears to be an effective strategy to achieve water conservation while limiting negative impacts on yield quantity and quality for cotton production in west-central Oklahoma.