Genetic resistance in crops is a cornerstone of disease management in agriculture. Such genetic resistance is often rapidly broken due to selection for virulence in the pathogen population. Here, we ask whether there are strategies that can prolong the useful life of plant resistance genes. In a modeling study, we compared four deployment strategies: gene pyramiding, sequential use, simultaneous use, and a mixed strategy.We developed a spatially explicit model for France and parameterized it for the fungal pathogen Puccinia striiformis f. sp. tritici (causing wheat yellow rust) to test management strategies in a realistic spatial setting. We found that pyramiding two new resistance genes in one variety was the most durable solution only when the virulent genotype had to emerge by mutation. Deploying single-gene-resistant varieties concurrently with the pyramided variety eroded the durability of the gene pyramid. We found that continuation of deployment of varieties with broken-down resistance prolonged the useful life of simultaneous deployment of four single-gene-resistant varieties versus sequential use. However, when virulence was already present in the pathogen population, durability was low and none of the deployment strategies had effect. These results provide guidance on effective strategies for using resistance genes in crop protection practice.