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Mosquitoes, deemed the deadliest creatures on Earth due to the diseases they transmit, have caused more fatalities than all recorded wars combined. Investigating the macroecology of mosquitoes on a continental scale is imperative for effective disease management and prevention. Our study utilized observational data from 17 sites within the National Ecological Observation Network across the United States. Extracting information from three NEON databases—mosquito samples, mosquito pathogen status, and weather statistics—we analyzed 45,000 labeled data points to elucidate the spatial distribution of mosquito abundance and its environmental determinants. A discernible biogeographic pattern of mosquito abundance emerged, in major natural ecosystems across the US, with the highest abundance observed in mid-latitudes. Our analysis revealed that wind speed and temperature exert significant controls, whereas air pressure and precipitation exhibited minimal influence over mosquito abundance across space. Specifically, temperature positively correlated with mosquito abundance, while wind speed displayed a negative association. Temporally, substantial inter-annual variability characterized mosquito abundance, with clear seasonal patterns observed at each site. Temperature emerged as the primary driver of seasonal fluctuations in mosquito abundance, with sites in middle latitudes exhibiting more pronounced seasonality compared to those at high and low latitudes, likely due to temperature fluctuations. This work, by comprehensively studying mosquitoes and their environmental controls, contributes to the development of targeted interventions, such as vector control programs and vaccine development, ultimately safeguarding human health and reducing the burden of mosquito-borne illnesses on human society.