Diffuse agricultural pollution is a leading contributor to surface water degradation, particularly in regions undergoing rapid land use change and agricultural intensification. In many developing countries, conventional assessment approaches fall short of capturing the spatial complexity and cumulative nature of multiple environmental drivers that influence surface water vulnerability. This study addresses this gap by introducing the Integral Index of Vulnerability to Diffuse Contamination (IIVDC), a spatially explicit, multi-criteria framework that combines the Analytical Hierarchy Process (AHP) with Geographic Information Systems (GIS). The IIVDC integrates six key indicators—slope, soil erodibility, land use, runoff potential, hydrological connectivity, and observed water quality—weighted through expert elicitation and mapped at high spatial resolution. The methodology was applied to the Guachal River watershed in Valle del Cauca, Colombia, where agricultural pressures are pronounced. Results indicate that 33.0% of the watershed exhibits high vulnerability and 4.3% very high vulnerability, with critical zones aligned with steep slopes, limited vegetation cover, and strong hydrological connectivity to cultivated areas. By accounting for both biophysical attributes and pollutant transport pathways, the IIVDC offers a replicable tool for prioritizing land management interventions. Beyond its technical application, the IIVDC contributes to sustainability by enabling evidence-based decision-making for water resource protection and land use planning. It supports integrated, spatially targeted actions that can reduce long-term contamination risks, guide sustainable agricultural practices, and improve institutional capacity for watershed governance. The approach is particularly suited for contexts where data are limited but spatial planning is essential. Future refinement should consider dynamic water quality monitoring and validation across contrasting hydro-climatic regions to enhance transferability.