Plant disease resistance often relies on simple “gene-for-gene” systems and, in the pathogen, a mutation in a single “avirulence” gene matching the plant resistance gene is sufficient to render the resistance ineffective. In agricultural systems, breeding for resistance is challenged by both the high evolutionary potential of the pathogen and the large scale of crop production; together, these factors encourage “breakdown” of novel sources of resistance soon after their deployment. Here, we established a four-year field experiment to evaluate the mechanisms and speed with which a fungal pathogen of oilseed rape, Leptosphaeria maculans renders ineffective the novel resistance gene Rlm7. The pathogen showed a very high evolutionary potential; the proportion of isolates in the population that were virulent against Rlm7 increased from 0 to 36% in four years. The experiment demonstrated that an extremely diverse range of molecular events leading to virulence, from more or less extensive nucleotide mutations or deletions to complete gene deletion, can occur in a single field. These results suggest that the genomic environment of the avirulence gene and the reproductive regime of the pathogen promote mutability at a single locus to produce virulence. Cropping practices that promote large pathogen populations and encourage sexual reproduction therefore favour rapid adaptation of the pathogen to the novel resistance.