Variable-rate application has great potential to reduce variability and increase yield by spatially optimizing agricultural inputs. In cotton, plant growth regulators (PGRs) control excessive growth and provide suitable plant height for harvest operations. This study evaluates the effect of variable-rate PGR application compared to constant-rate application to reduce yield spatial variability and increase yield. The variable-rate approach was carried out in 2020 based on zonal applications defined by clustering analysis using soil electrical conductivity, vegetation indexes, and yield maps. Application doses and timings were determined by integrating plant height measurements for the whole field in 2019 and by zone in 2020. To compare the two procedures, cultivar and plant populations were kept constant; fertilization and accumulated rain were similar in both seasons. A reduction in yield spatial variability due to the zonal application was observed, with yield coefficient of variation (CV) decreasing from 18% in 2019 to 12% in 2020. Spatial and temporal analysis of Normalized Difference Vegetation Index satellite images showed higher CV values in 2019 (constant-rate) reaching 30% at the end of the season, whereas in 2020 (variable-rate) CV was constant (approximately 10%). Cotton yield increased from 3.5 to 4.3 t ha-1 between 2019 and 2020, which can be partially attributed to the variable-rate approach. The variable-rate approach based on application zones and plant height measurements was a viable strategy for reducing yield spatial variability and likely increasing yield in a highly variable cotton field.