Herbicides have been widely used to manage woody vegetation, but quantification of their effects is often lacking. We documented the impacts of a commonly used clopyralid + aminopyralid + triclopyr herbicide blend on Prosopis velutina Woot. in grazed Sonoran Desert grasslands in southern Arizona. Similar to other applications of comparable herbicide blends in the region, we recorded only modest and short-term impacts. P. velutina mortality was 7%. Foliar cover declined to 9.2% ± 0.80% the month following treatment and was comparable across size classes. Cover reductions persisted for ∼2 yr, by which time it was comparable on treated and control plants (66.9% and 69.3%, respectively). On the basis of eddy covariance tower monitoring of carbon and water flux, soil temperature, and soil moisture, we suggest how knowledge of diurnal and seasonal changes in physiological activity (e.g., evapotranspiration, gross primary production) and environmental conditions may help identify more optimal times to apply herbicides to improve their efficacy. Future research should explore P. velutina response to herbicides at various levels of photosynthetic activity in response to soil temperature and soil moisture in the subtropical North American Monsoon climate system of the Sonoran Desert. From a broader ecosystems trophic perspective, our results also suggest a need to ascertain how herbicide-induced reductions in P. velutina pod and seed production may impact native herbivore communities.