In the semiarid Texas Rolling Plains, the growth and yield of cotton (Gossypium hirsutum L.) is driven by the amount of water available to the crop through irrigation and precipitation. A field study was conducted in 2012 and 2013 at Chillicothe, TX, to investigate the growth, yield, water use efficiency (WUE), and spectral reflectance responses of cotton. A split-split plot design with three replications was used with irrigation as the main plot (three irrigation levels and dryland), tillage (no tillage and conventional tillage) as the subplot, and cultivars (PHY499, DP1044, PHY375, and FM9170) as the sub-subplot treatments. Plant height, lint yield, WUE, and fiber quality were significantly affected by irrigation and irrigation × cultivar interaction. Increasing irrigation level resulted in a linear increase in lint yield and WUE. the irrigation × cultivar interaction showed that the 90% evapotranspiration (ET) replacement treatment with PHY375 produced the greatest lint yield and WUE. Tillage did not significantly affect lint yield, WUE, or fiber quality. Increasing irrigation resulted in a linear increase in fiber length and strength, and a linear decrease in fiber micronaire. Two vegetation indices, normalized difference vegetation index (NDVI) and normalized difference water index (NDWI) were calculated using spectral reflectance measurements in this study. the NDWI increased steadily for all irrigation treatments during the measurement period. However, NDVI exhibited little change during the peak growth period between 79 and 89 d aft er planting. We suggest further investigation on using NDWI for irrigation management for cotton in the Texas Rolling Plains.