Pesticide use is a key component of efficient crop production, but is associated with a suite of costs. Understanding the main drivers of pesticide use will help us target research to develop effective alternatives. Although economic models predict, and empirical tests confirm, that the value of the crop being protected is an important determinant of between-crop variation in pesticide use, previous tests of this prediction have examined only modest numbers of crops and have not assessed the relative importance of crop value versus ecological determinants of pesticide use. Here we analyze variation in pesticide use across 93 crops grown in California, USA. We examine the joint roles of crop value and ecological determinants of pesticide use, including (i) the number of pest species associated with each crop; (ii) the distinction between annual vs. perennial crops; and (iii) the distinction between unprocessed vs. processed crops. As predicted, crop value was the dominant driver of the use of pesticides directed at arthropods and at plant pathogens, explaining 52.7% and 54.6% of total deviance, respectively. Ecological determinants of pesticide use were, however, also detected. Pesticide use was greater on crops that hosted a larger number of arthropod pest species (r = 0.32) or plant pathogen species (r = 0.29); for these pest groups, we saw no differences in pesticide use between annual vs. perennial crops, or processed vs. unprocessed crops. Perhaps surprisingly, crop value failed to explain the substantial between-crop variation in use of pesticides targeting weeds (1.7% of deviance explained, n.s.). Instead, an ecological factor, whether the crop was an annual versus a perennial plant, was the most important predictor of pesticide use against weeds, with more frequent applications on perennial crops. We conclude that both economic and ecological drivers influence the magnitude of potential crop losses, thereby shaping farmer pest control practices.