An experiment was conducted in controlled environments to evaluate the effects of relative humidity (RH) and soil moisture (SM) on fluroxypyr efficacy on kochia and Palmer amaranth. Plants were grown in growth chambers with constant RH of 35 or 90 ± 5% and 28/23 C day/night temperature. Within each growth chamber, plants were grown in SM regimes of either −20 or −40 kPa. When plants were 8 to 10 cm tall, fluroxypyr was applied at 26, 52, 78, or 104 g ae ha−1; a nontreated control was included. At 21 days after treatment, control of both species increased with increasing fluroxypyr rate. Kochia control was not affected by RH, but control was greater when plants were grown in moist soil (−20 kPa) than in dry soil (−40 kPa). Conversely, Palmer amaranth control was greater when plants were grown at 90% RH than at 35% RH, but control did not differ between moist and dry soils. This study showed that the influence of environmental factors on fluroxypyr efficacy on kochia and Palmer amaranth is species dependent.