Utilizing Unmanned Aerial Vehicle (UAV) multispectral technology offers a non-destructive and efficient approach to monitoring plant health and stress responses by analyzing reflectance data across various wavelengths. This study integrates UAV-based multispectral imagery with ground-measured sample data to evaluate the impact of atrazine (ATR) on chlorophyll a, chlorophyll b, carotenoids, and anthocyanins in Red Cos lettuce. The results indicate a significant increase (p < 0.05) in ATR concentration in lettuce with soil application, leading to notable reductions in pigment concentrations. Heatmap analysis reveals that EVI shows the strongest negative correlations with pigment classes (coefficients ranging between −0.75 to −0.85), while NDVI, GNDVI, and BNDVI exhibit the strongest positive correlations with pigments (coefficients > 0.75). These findings highlight the potential of this innovative technique in predicting pigment concentrations and emphasize its importance in monitoring pesticide effects for sustainable agriculture.