Huisache (Vachellia farnesiana [L.] Wight & Arn.) is a woody species native to the western hemisphere that can invade a variety of native rangeland habitats around the world. In South Texas, it is native yet increasing in density and range while displacing more desirable forage plants, and because it resprouts prolifically it has been difficult to control. We therefore attempted to characterize optimal timing and environmental conditions for herbicide control. We collected weather data in four huisache-invaded pastures along the Texas Coastal Bend and recorded the average huisache phenological stage at those pastures each month. We also analyzed root crown total nonstructural carbohydrate (TNC) and huisache mortality resulting from herbicide treatment each month between April 2012 and November 2014. Huisache mortality and TNC data were analyzed using a randomized complete block analysis of variance, with post hoc tests to separate means; Akaike's information criterion determined best-fit models for mortality data. Root crown TNC increased during May, August, and December, indicating downward translocation and the potential for increased mortality of treated plants. Actual mortality was greatest during the months of May, September, October, and November. The best fit model for mortality was a sixth-order polynomial function of mortality versus month; when month was removed as a model factor, the best fit model was a quadratic function of soil temperature (peaking at ≈24.5°C), combined with a quadratic function of phenology (highest at full canopy stage). These results indicate that huisache is best treated with chemicals when soil temperature is near 24.5°C and during the full canopy stage. In the coastal plains of South Texas these variables coincide with two windows of optimal mortality for huisache treatment: May and September–November.