The reduction in biodiversity through land use changes due to urbanization and agricultural intensification, appears linked to major epidemiological changes in many human diseases. Increasing disease risks and the emergence of novel pathogens appear to result from increased contact between wildlife, domesticated animals and humans. We investigate how increasing human domination of the environment may favor generalist and synanthropic rodent species and affect the diversity and prevalence of rodent-borne pathogens in Southeast Asia, a hotspot of threatened and endangered species and emerging infectious diseases. We used extensive pathogen survey data on rodents from seven sites in mainland Southeast Asia in conjunction with present and past land cover analysis. At low spatial resolution across sites, we found that rodent-borne pathogen richness is negatively associated with increasing urbanization, characterized by increased habitat fragmentation, agriculture cover and deforestation. However at high spatial resolution among sites, we found that some major pathogens are favored by certain environmental characteristics associated with human domination of landscapes, including irrigation, habitat fragmentation, and increased agricultural land cover. In addition, synanthropic rodents, many of which are important pathogen reservoirs, were found favoured in fragmented and human-dominated areas, which may ultimately enhance the opportunities for zoonotic transmission and human infection by certain pathogens.