In eastern inland Australia, the significant redistribution of water in the Murray River system for irrigated agriculture from the late nineteenth century created new ecological dynamics. At the same time, scientific research into mosquito-borne diseases also increased. Scientific proof of the life cycle of malaria in the late nineteenth century, and subsequent research into this and other mosquito-borne diseases, changed people’s relationships with watery landscapes, including irrigation areas, as well as with mosquitoes. Wetlands were no longer just dangerous to visit but could come out into the world, onto farms, and into homes via these insects. Within these contexts, this article examines changing understandings of mosquitoes and irrigation systems in light of a series of investigations into the possibility of an outbreak of malaria in the Murrumbidgee Irrigation Area between 1919 and 1945. Using the concept of imagined ecologies, it examines the way that particular understandings of nonhumans were and are world-making. It particularly analyzes the shifting biocultural terrains of the borders between agriculture and “nature,” and the home and nonhumans, as well as approaches to race and health, as mosquitoes were now seen to bring tropical diseases to the climatically and socially idealized temperate inland. Underpinned by powerful political and social goals, these watery farming areas could not be drained like other wetlands, presenting possible new medical, ecological, and ideological challenges.