Tan spot, caused by Pyrenophora tritici-repentis (Died.) Drechs, is a serious constraint on wheat yields in the Southern Cone region of South America. A 2-year experiment was conducted to evaluate fungicide deposition, disease development and grain yield. Three spray nozzles were evaluated: an air-induction flat fan (AI), a wide-angle flat fan (TT), and an extended-range flat fan (XR). A systemic fungicide containing azoxystrobin and cyproconazole was used in both years. Tan spot severity and the area under non-green leaf area disease progress curve (AUNGLA) were analysed. There were no significant differences in deposition among nozzles, and no significant interactions between nozzles and leaf layers in the first year. In both years, AUNGLAs were similar for the three nozzles types, and the tan spot severity in untreated plots was significantly higher than in fungicide-applied plots. Grain yield was higher in the fungicide-applied plots, and there were no significant differences among nozzles in both years. Droplet size had no effect on the fungicide’s efficacy for tan spot control in Uruguay across three susceptible wheat cultivars. The use of drift-reducing nozzles and a systemic fungicide in these trials led to satisfactory performance for spray deposition, canopy penetration and control of the tan spot disease of wheat in the same way as expected from conventional nozzles.