Precise control over pesticide spraying by agricultural drones requires fundamental research of multiphase flow, heat and mass transfer of liquid droplets in downwash flow. In this study, water was used as a carrier agent in pesticide formulations, in which the liquid droplets exhibit a Newtonian fluid behavior. A general computational fluid dynamics (CFD) model that characterizes propeller motion coupled with droplet evaporation and deposition was developed. The downwash flow generated by the propeller rotation was simulated using a multiple reference frame method along with the SST-k-ω turbulence model. Spraying of liquid droplets was simulated using a discrete phase model. The flow model validation was conducted by comparing the simulated velocities with experimental data, and the spray model validation was completed by a comparison of droplet depositions from CFD predictions and experiments. The results indicated that the droplet deposition fluctuates with an increase of propeller speed, and that both temperature and relative humidity affect the droplet deposition. In addition, the relation between the number of particles and the impact velocity was identified quantitatively, impact velocity with respect to particle diameter was predicted, and the effects of surface inclination, surface roughness, and crosswind speed on droplet deposition were analyzed. Moreover, an in-depth discussion about the intrinsic relation between downwash flow and droplet spraying was conducted.