Simplification of agricultural landscapes is expected to have positive effects on many crop pests and negative effects on their natural enemies, potentially leading to increased pest pressure, decreased crop yield, and increased insecticide use. While many intermediate links in this causal chain have empirical support, there is mixed evidence for ultimate relationships between landscape simplification, crop yield, and insecticide use, especially at large spatial and temporal scales. We explored relationships between landscape simplification (proportion of a county in harvested cropland) and insecticide use (proportion of harvested cropland treated with insecticides), using county-level data from the US Census of Agriculture and a variety of standard and spatiotemporal regression techniques. The best model indicated that insecticide use across the US has increased between 1997 and 2012, was strongly dependent on the crops grown in a county, increased with average farm income and size, and increased with annual growing degree days. After accounting for those variables, and other unidentified spatial and temporal structure in the data, there remained a statistically significant, moderate, positive relationship between insecticide use and landscape simplification. These results lend general support to the causal chain outlined above, and to the notion that a landscape perspective is useful for managing ecosystem services that are provided by mobile organisms and valuable to agriculture.