Freshwater ecosystems are the most vulnerable environments worldwide and the most biodiverse, providing essential ecosystem services. The role of land management in agriculture is paramount with the dramatic increase in pesticides: two million tonnes used worldwide (47.5% herbicides, 29.5% insecticides, and 17.5% fungicides) are jeopardising freshwater ecosystems. Concerns about the risk of pesticide contamination from viticulture have led to implementing nature-based mitigation measures (buffer strips and hedgerows) and technical improvements. The general aim is to assess spatial proximity among vineyards and river networks within the Prosecco DOCG area to identify potential critical areas for pesticide contamination. Specific objectives are: i) mapping vineyards within the Prosecco DOCG area, ii) identifying river banks with a higher probability of experiencing pesticide contamination, and iii) mapping critical areas potentially affected by pesticide contamination. Spatial modelling was based on very high geometric resolution ortophotos (50 cm), LiDAR data (1 m), and morpho-hydrological parameters of the river network. Proximity and morpho-hydrological modelling showed that due to little distance from Prosecco cropland (5–20 m), freshwater ecosystems may be affected in different basins by spray drift pesticide contamination. Distances between vineyards and streams were shown to be critical, as 35.7% and 13.9% of river banks were within 20 m and 5 m distance from vineyards, respectively. Furthermore, 52% of basins presented river banks intersecting vineyards at 5 m, while 37% were within 20 m distance. Such hotspots should be investigated in the field for watershed-based quality assessment. However, mitigation scenarios indicate that spray drift contamination might be reduced by 75%, minimising the effect from 20 m to 5 m distance from vineyards and, therefore, avoiding reaching part of riparian and aquatic ecosystems. Geovisualisation of river banks proximity at watershed level offered insight into area with high probability of experiencing pesticide contamination from vineyards due to spray drift.