The emerging amphibian disease chytridiomycosis is caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd). Amphibian populations and species differ in susceptibility to Bd, yet we know surprisingly little about the genetic basis of this natural variation. MHC loci encode peptides that initiate acquired immunity in vertebrates, making them likely candidates for determining disease susceptibility. However, MHC genes have never been characterized in the context of chytridiomycosis. Here, we performed experimental Bd infections in laboratory-reared frogs collected from five populations that show natural variation in Bd susceptibility. We found that alleles of an expressed MHC class IIB locus associate with survival following Bd infection. Across populations, MHC heterozygosity was a significant predictor of survival. Within populations, MHC heterozygotes and individuals bearing MHC allele Q had a significantly reduced risk of death, and we detected a significant signal of positive selection along the evolutionary lineage leading to allele Q. Our findings demonstrate that immunogenetic variation affects chytridiomycosis survival under controlled experimental conditions, confirming that host genetic polymorphisms contribute to chytridiomycosis resistance.