Disease can generate intense selection pressure on host populations, but here we show that acquired immunity in a population subject to repeated disease outbreaks can impede the evolution of genetic disease resistance by maintaining susceptible genotypes in the population. Interference between the life‐history schedule of a species and periodicity of the disease has unintuitive effects on selection intensity, and stochasticity in outbreak period further reduces the rate of spread of disease‐resistance alleles. A general age‐structured population genetic model was developed and parameterized using empirical data for phocine distemper virus (PDV) epizootics in harbor seals. Scenarios with acquired immunity had lower levels of epizootic mortality compared with scenarios without acquired immunity for the first PDV outbreaks, but this pattern was reversed after about five disease cycles. Without acquired immunity, evolution of disease resistance was more rapid, and long‐term population size variation is efficiently dampened. Acquired immunity has the potential to significantly influence rapid evolutionary dynamics of a host population in response to age‐structured disease selection and to alter predicted selection intensities compared with epidemiological models that do not consider such feedback. This may have important implications for evolutionary population dynamics in a range of human, agricultural, and wildlife disease settings.