This study aimed to evaluate the influence of unmanned aerial vehicle (UAV) flight settings on spray quality and herbicide efficacy in wheat (Triticum aestivum L.) under field conditions. The experiment was conducted over two growing seasons with four UAV-based treatments (two flight heights: 1.5 and 2.5 m; two flight speeds: 3 and 5 m s-1) and a non-treated control to assess the effect of flight settings on spray quality. Two herbicide mixtures were tested applied at 30 L ha-1. The analyzed spray quality parameters included droplet deposition (µL cm-2), surface coverage (%), droplet density (drops cm-2), and volume median diameter (VMD). At the same time, herbicide efficacy was assessed based on weed density and fresh weed mass reduction. In the first growing season (2022), treatments applied at the lower flight height (h = 1.5 m) resulted in superior spray quality, with maximum droplet deposition exceeding 0.70 µL cm⁻² and surface coverage reaching up to 11.2% (1.5 m at 3 m s-1 and 1.5 m at 5 m s-1). In contrast, in the second season (2023), the highest herbicide efficacy was observed at the higher flight height of 2.5 m (3 and 5 m s-1), despite lower deposition values (0.19-0.27 µL cm-2). At higher flight heights and speeds, finer droplets were produced, with the VMD decreasing to 354 µm in 2022 and 275 µm in 2023, confirming the influence of increased dispersion and airflow on droplet size during UAV spraying. The systemic activity of iodosulfuron-methyl-sodium + amidosulfuron + mefenpyr-diethyl appeared to compensate for reduced initial deposition and coverage. Both herbicides achieved high efficacy when applied via UAV, with 1.5 m at 5 m s-1 and 2.5 m at 5 m s-1 showing the most consistent weed control. Lamium purpureum was the dominant and most persistent weed species across both years, showing the lowest response to herbicide treatments. These findings demonstrate that conventional herbicide formulations can be effectively applied using UAV systems when flight settings are properly optimized, highlighting their potential for aerial application in wheat production. Further research should focus on the development and registration of UAV-specific herbicide formulations.