Four types of nozzles were tested on large-scale trials with a 40 m2 plot unit size. The Avi Twin 110-01 (80 L ha−1), 110-02 (160 L ha−1), 110-03 (240 L ha−1), and 110-04 (320 L ha−1) symmetric double fan injector nozzles were tested during the 2020/2021 and 2021/2022 growing seasons. This study aimed to evaluate the performance of spray nozzles with regard to deoxynivalenol (DON) accumulation in durum wheat grains. Artificial inoculation with Fusarium spp. was performed after durum heads were protected with fungicide. The percentage of heads covered with fungicide droplets, grain yield, yield-related traits, technological quality parameters, and concentrations of DON were determined. Compared to the control (without fungicide treatment), the Avi Twin 04 nozzle caused a reduction of 45.0% in the DON concentration on average across both growing seasons. This positively corresponded to the percentage of heads covered with fungicide droplets, which was highest when this nozzle was utilized. In both trial years, the DON reduction caused by the 110-04 twin nozzle was higher than that caused by the 110-01 nozzle. Treatment with the 110-04 nozzle more effectively improved the grain yield, 1000-kernel weight, and test weight compared to treatment with the 110-01 nozzle and the untreated control. The differences in technological quality were less pronounced when different spray nozzles were used.