Agrochemicals have numerous negative impacts on human health, ecosystem services, and ecological communities. Thus, their efficient use is an economic and ecological priority. Simplified landscapes may enhance insecticide use by reducing natural enemies and increasing connectivity of crops, but empirical tests of this theory are inconclusive. We explored the relationship between landscape simplification and insecticide use using longitudinal data from USDA Census of Agriculture spanning six censuses and 25 years (1987, 1992, 1997, 2002, 2007, 2012) for nearly 3000 counties across the continental United States. The effect of landscape simplification was highly variable spatially and temporally. Landscape simplification was consistently correlated with increased insecticide use in some regions, but not in others. Our results indicate that the landscape-simplification-insecticide-use relationship is dynamic, and that national land use policy would benefit from actions that adequately reflect the spatial differences in the importance of landscape complexity to insecticide use.