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Huisache (Acacia farnesiana [L.] Willd.) is expanding in range and density and displacing more desirable forage species in South Texas. We characterized optimal timing and environmental conditions for effective herbicide control by analyzing root Total Nonstructural Carbohydrate (TNC) content and mortality of sprayed trees over two years. Each month between April 2012 and November 2014, five shrubs in each of four different study sites were excavated, and the root crowns were collected and analyzed for TNC. In addition, two herbicide formulations were foliar-applied to five to ten shrubs every month at the four sites from July 2012 to November 2014, and mortality was evaluated following two growing seasons. Data were analyzed using a randomized complete block design ANOVA, and Akaike�s Information Criterion (AIC) was used to determine the best-fit model for mortality. We found significant TNC increases (compared to the prior month) during May, August, and December. Herbicide-induced mortality was greatest during the months of May, October, November, and September. The best fit model for mortality was a sixth-order polynomial function of mortality vs. month; when month was removed as a parameter, the best fit model was a quadratic function of mortality vs. soil temperature, combined with a quadratic function of mortality vs. phenology. These results indicate two windows in which to chemically treat huisache to achieve high mortality in the coastal plains of South Texas:� spring (especially May) and autumn (especially October and November). Besides month (which can have variable environmental conditions), high huisache mortality rates can also be expected when soil temperature at 0.3 m is at or near a peak of 24.5�C, during the full canopy stage.