The gradual depletion of the Ogallala Aquifer under the Southern High Plains of Texas during the past fifty years has resulted in reduced well capacities for cotton irrigation. Water table declines have already led some to shift from irrigated to dryland farming, and many of the remaining wells cannot provide enough water for full irrigation. The present study evaluated the effectiveness of the synthetic cytokinin CPPU (N-(2-chloro-4-pyridinyl)-N’-phenylurea) on the stimulation of lateral root production and enhancement of cotton yields under dryland conditions. Seed treatments of 250 µmol/mol or seedling sprays of 5 µmol/mol at the cotyledon stage, increased lateral root production. Cotton yield increases associated with the increased rooting ranged from 8 to 20% in three years of field studies under dryland conditions. The greatest yield increases were associated with dry shallow soils. Evaluation of water-deficit stress levels in untreated and CPPU-treated cotton showed reduced water-deficit stress levels throughout the growing season in the CPPU-treated cotton. This study showed that application of CPPU to cotton, early in development, has the potential to reduce water stress and increase yields.