Climate change is altering global patterns of precipitation and temperature variability, with implications for parasitic diseases of humans and wildlife. A recent study confirmed predictions that increased temperature variability could exacerbate disease, because of lags in host acclimation following temperature shifts. However, the generality of these host acclimation effects and the potential for them to interact with other factors have yet to be tested. Here, we report similar effects of host thermal acclimation (constant versus shifted temperatures) on chytridiomycosis in red-spotted newts (Notophthalmus viridescens). Batrachochytrium dendrobatidis (Bd) growth on newts was greater following a shift to a new temperature, relative to newts already acclimated to this temperature (15°C versus 25°C). However, these acclimation effects depended on soil moisture (10, 16 and 21% water) and were only observed at the highest moisture level, which induced greatly increased Bd growth and infection-induced mortality. Acclimation effects were also greater following a decrease rather than an increase in temperature. The results are consistent with previous findings that chytridiomycosis is associated with precipitation, lower temperatures and increased temperature variability. This study highlights host acclimation as a potentially general mediator of climate–disease interactions, and the need to account for context-dependencies when testing for acclimation effects on disease.