Cotton is a vital component of the economies of Mid-South states. Producers and landowners are looking for ways to reduce the variability of irrigated yields, and soil apparent electrical conductivity (ECa) is a readily obtained parameter that can indicate soil variability. A study was conducted in 2011 and 2012 at the Fisher Delta Research Center in Portageville, MO, with the objective to determine the impact of soil spatial variability on yield and irrigation water use efficiency for cotton. Observed ECa values were low, consistent with average sand contents that ranged from 59 to 82% in the upper 0.76 m of the soil profile. Spatial autocorrelation was present in the data and thus spatial analyses were used. In 2011, yields for two treatments were not significantly different from the mean field effect; however, the ECa effect was significant, indicating that soil variability impacted yield more than irrigation differences for the two treatments. In 2012, yields for four of the six treatments were significantly different from the mean field effect; however, the ECa effect was not significant. A quadratic equation was fit to the combined data from irrigated and rainfed plots in 2012. The resulting equation had a maximum of 3,372 kg ha-1 at 135 mm total irrigation and the median observed ECa value (3.0 mS m-1). Future efforts will include additional fields and environments, which should increase the understanding of the impact of soil variability and allow for improved selection of optimum management zones for site specific application of water and other inputs.