Anthropogenic land use change, including agriculture, can alter mosquito larval habitat quality, increase mosquito abundance, and increase incidence of vector-borne disease. Rice is a staple food crop for more than half of the world's population, with ∼1% of global production occurring within the United States (US). Flooded rice fields provide enormous areas of larval habitat for mosquito species and may be hotspots for mosquito-borne pathogens, including West Nile virus (WNV). West Nile virus was introduced into the Americas in 1999 and causes yearly epidemics in the US with an average of approximately 1,400 neuroinvasive cases and 130 deaths per year. We examined correlations between rice cultivation and WNV disease incidence in rice-growing regions within the US. Incidence of WNV disease increased with the fraction of each county under rice cultivation in California but not in the southern US. We show that this is likely due to regional variation in the mosquitoes transmitting WNV. Culex tarsalis was an important vector of WNV in California, and its abundance increased with rice cultivation, whereas in rice-growing areas of the southern US, the dominant WNV vector was Culex quinquefasciatus, which rarely breeds in rice fields. These results illustrate how cultivation of particular crops can increase disease risk and how spatial variation in vector ecology can alter the relationship between land cover and disease.