Plant viruses account for enormous agricultural losses worldwide, and the most robust way to combat this is to identify genetic material conferring resistance to those pathogens. Here, we screen a large panel of Arabidopsis thaliana natural inbred lines for four disease-related traits in response to infection by nave and evolved strains of the natural pathogen turnip mosaic virus (TuMV). Using GWAS, we detected a strong, replicable association between a 50kb region on chromosome 2 and a 10-fold increase in relative risk of necrosis in response to infection. The region contains several plausible causal genes, as well as abundant structural variation that could be either a driver or a consequence of the disease resistance locus. Susceptible alleles are found worldwide, and their distribution is consistent with a trade-off between resistance during viral outbreaks and a cost of resistance otherwise, leading to negative frequency-dependent selection.