African rue is an exotic, herbaceous perennial established in several western states that tolerates harsh, water-stressed conditions. The influence of water-deficit stress on herbicide response and subsequent herbicide fate within the plant were compared. African rue seedlings were deprived of water for 0 to 7 d to establish a gradient of water-deficit levels before treatment with hexazinone, imazapyr, or metsulfuron. At herbicide application, water-deficit treatments reduced plant water potential values from −1.0 MPa to −4.7 MPa, causing concomitant reductions in photosynthesis. Thirty-five days after treatment, dry weight of imazapyr- and metsulfuron-treated plants was reduced in plants exposed to more than 4 d water-deficit stress before herbicide application. In contrast, hexazinone-treated plants had less dry weight than water-stressed, nonsprayed control plants regardless of water-deficit stress. Seventy-two hours after herbicide application, African rue leaves absorbed from 5 to 42% of herbicide applied; however, herbicide absorption did not correlate to efficacy. Less than 12% of absorbed herbicide translocated out of the treated leaf, regardless of herbicide. Radiolabel translocated from the treated leaf to acropetal or root tissue did not differ among herbicide treatments, regardless of water deficit before herbicide application. However, compared to other herbicides, translocation to basipetal shoot tissue was greatest in imazapyr-treated seedlings with the largest water deficit at herbicide application. Increased translocation occurred at higher levels of water stress than were necessary to increase herbicide efficacy, suggesting differential translocation was not involved in enhanced efficacy. In summary, African rue seedlings absorbed and mobilized three different herbicides at all levels of water-deficit stress. In addition, the efficacy of metsulfuron and imazapyr increased as water-deficit stress increased, but efficacy of hexazinone was not influenced by plant water status. This unusual relationship between water-deficit stress and herbicide performance may enable improved African rue management under stressful environments.