Precious groundwater resources across the United States have been contaminated due to decades-long nonpoint-source applications of agricultural chemicals. Assessing the impact of past, ongoing, and future chemical applications for large-scale agriculture operations is timely for designing best-management practices to prevent subsurface pollution. Presented here are the results from a series of regional-scale vulnerability assessments for the San Joaquin Valley (SJV). Two relatively simple indices, the retardation and attenuation factors, are used to estimate near-surface vulnerabilities based on the chemical properties of 32 pesticides and the variability of both soil characteristics and recharge rates across the SJV. The uncertainties inherit to these assessments, derived from the uncertainties within the chemical and soil data bases, are estimated using first-order analyses. The results are used to screen and rank the chemicals based on mobility and leaching potential, without and with consideration of data-related uncertainties. Chemicals of historic high visibility in the SJV (e.g., atrazine, DBCP [dibromochloropropane], ethylene dibromide, and simazine) are ranked in the top half of those considered. Vulnerability maps generated for atrazine and DBCP, featured for their legacy status in the study area, clearly illustrate variations within and across the assessments. For example, the leaching potential is greater for DBCP than for atrazine, the leaching potential for DBCP is greater for the spatially variable recharge values than for the average recharge rate, and the leaching potentials for both DBCP and atrazine are greater for the annual recharge estimates than for the monthly recharge estimates. The data-related uncertainties identified in this study can be significant, targeting opportunities for improving future vulnerability assessments.