Emerging infectious diseases are one of the greatest threats to global biodiversity. Chytridiomycosis in amphibians is perhaps the most extreme example of this phenomenon known to science. Translocations are increasingly used to fight disease-induced extinctions. However, many programmes fail because disease is still present or subsequently establishes in the translocation environment. There is a need for studies in real-world scenarios to test whether environmental manipulation could improve survival in populations by generating unfavourable environmental conditions for pathogens. Reintroductions of amphibians impacted by chytridiomycosis into environments where the disease persists provide a scenario where this paradigm can be tested. We tested the hypothesis that manipulating environmental salinity in outdoor mesocosms under near-identical environmental conditions, present in a nearby translocation programme for an endangered amphibian, would improve survival and determine the mechanisms involved. One hundred and sixty infected and 288 uninfected, captive-bred, juvenile frogs were released into 16 outdoor mesocosms in which salinity was controlled (high- or low-salinity treatment). The experiment was run for 25 weeks from the mid-austral winter to the mid-austral summer of 2013 in a temperate coastal environment, Australia. Increasing salinity from c. 0.5 ppt to 3.5–4.5 ppt reduced pathogen transmission between infected and uninfected animals, resulting in significantly reduced mortality in elevated salt mesocosms (0.13, high-salt vs. 0.23, low-salt survival at 23 weeks). Increasing water temperature associated with season (from mean 13 to 25°C) eventually cleared all surviving animals of the pathogen. Synthesis and applications. We identified a mechanism by which environmental salinity can protect amphibian hosts from chytridomycosis by reducing disease transmission rates. We conclude that manipulating environmental salinity in landscapes where chytrid-affected amphibians are currently translocated could improve the probability of population persistence for hundreds of species. More broadly, we provide support for the paradigm that environmental manipulation can be used to mitigate the impact of emerging infectious diseases.