Palmer amaranth can grow 4.2 mm in height per degree day; hence, delays of a few days in weed control deployment can result in applications of herbicides to weeds that are larger than those for which the herbicide label recommends. Therefore, it is critically necessary to understand the effect of plant size at the time of herbicide application in conjunction with herbicide spray solution and nozzle type pairings on the effectiveness of weed management programs in the Enlist E3 and XtendFlex production systems. Field experiments were conducted in 2020, in no-crop conditions, at two locations in Arkansas, to evaluate the influence of Palmer amaranth size on its control with glufosinate, dicamba, and 2,4-D applied alone and in mixture with specific nozzle pairings as mandated by label requirements. Also, a laboratory experiment was conducted to evaluate the droplet size and velocity of the spray solutions and nozzles used in the field experiments. A 5- and 10-percentage point reduction in control was observed when dicamba (66%) and 2,4-D (63%) were applied alone, respectively, compared with those herbicides mixed with glufosinate (71% and 73%, respectively). Palmer amaranth density increased to 55, 73, 100, 115, and 140 plants m−2 when plants were sprayed at heights of 15, 25, 41, 61, and 76 cm, respectively, compared with plants that were sprayed when they were 5 cm tall (9 plants m−2). Nozzle type did not affect weed control or density. The percentage of driftable fines increased when a mixture of glufosinate and 2,4-D were used compared with 2,4-D alone. Effective short-term and long-term chemical control of Palmer amaranth will require growers to correctly time their weed management practices and overlay residuals, and expect the need for sequential applications.