UNLABELLED: Climate change is predicted to increase the spread of mosquito-borne viruses, but genetic mechanisms underlying the influence of environmental variation on the ability of insect vectors to transmit human pathogens is unknown. In response to a changing climate, mosquitoes will experience longer periods of drought. An important physiological response to dry environments is the protection against dehydration, here defined as desiccation tolerance. While temperature is known to impact interactions between mosquito and virus, the role of dehydration remains unknown. We identified two genetically diverse lines of the mosquito IMPORTANCE: Climate change will have profound impacts on the burden of viruses transmitted by mosquitoes. While we know how changes in temperature impact mosquito physiology and dynamics of viral replication within the mosquito, there is a complete lack of knowledge in how low humidity, or drought tolerance, will impact interactions between mosquitoes and arboviruses. Understanding how drought tolerance will alter mosquito infection with arboviruses is critical in predicting and preventing the impact that climate change will have on mosquito-borne viruses. This work demonstrates a functional link between dehydration tolerance and midgut infection. This knowledge significantly enhances our understanding of how the predicted increase in droughts could impact the dynamics of mosquito-borne viruses.