Abstract This study traces the evolution of social–environmental models of malaria control in Northwest Argentina. Beginning in the 1890s, the rationale for malaria control hinged on a narrative that placed malaria as the root cause of the Northwest's chronic backwardness. Insalubrious rural and urban landscapes, underutilized agricultural potential, unproductive labor, and even racial decay were all bound together as a public health problem. The framework for understanding malaria in the environment was derived from miasmatic theory and medical geography, anchoring the disease firmly in particular landscapes. Wetlands, representing both economic waste and a public health hazard, were singled out as targets for reclamation. Thus ‘environmental sanitation’ techniques, especially wetland drainage, became the preferred strategy for the federal government's malaria campaign, initiated in 1907. The ‘socio-ecological’ orientation of the Italian malaria campaign under Fascism, in which large-scale wetland reclamation for malaria control seemed to produce a comprehensive transformation of rural land and life, had a strong influence in Argentina, further entrenching environmental sanitation methods. By the 1930s, however, it became apparent that Italy's wetlands served poorly as landscape analogues for Argentina's Northwest. In particular, the main mosquito vector in the region turned out not to be a stereotypical ‘swamp breeder,’ rendering pointless most wetland drainage efforts. A counter-model, which adopted the framework of ecological science, proved to be more sensitive to the behaviors and microenvironments of different mosquito species, while disentangling malaria control from the broader and mostly unrealistic social development goals of the older model.