Introduction: In the literature, studies of the relationship between pesticide exposure and various diseases face the challenge of assessing exposure, particularly in a retrospective manner. Cultivation-exposure matrices (CEMs) were developed to address this challenge. Objective: Our method combines CEMs with land-use data from agricultural censuses to determine geographic indicators of environmental and occupational exposure. We illustrate this approach for two active ingredients. Method: CEMs for four crops are used (straw cereals, corn, potatoes, and grapes). They describe three groups of pesticides, their chemical families, and their active ingredients based on three indicators per region and per period since 1960. These data are combined with agricultural censuses (1979, 1988, 2000, 2010) to calculate environmental and occupational exposure indicators for each canton in metropolitan France. Two active ingredients (chlortoluron, pyrimicarb) illustrate this methodology, and the results are compared with pesticide purchase data (National Database of Plant Protection Product Sales by Distributors [BNV-D]). Results: Both active ingredients show temporal and spatial trends. The proportion of areas/farms treated with pyrimicarb increased between 1979 and 2010, unlike chlortoluron. The North has the highest values for pyrimicarb; this gradient is supported by strong spatial autocorrelation. The patterns are more varied for chlortoluron. Comparisons with purchase data show high correlations (≥ 0.80). Conclusion: Combining MCE data with agricultural census data describes pesticide exposure at a fine geographic level (the canton). This approach allows for the identification of spatial trends—confirmed by comparison with pesticide purchase data—as well as temporal trends.