The combination of major resistance genes with quantitative resistance factors is hypothesized as a promising breeding strategy to preserve the durability of resistant cultivars. In three pathosystems, experimental data demonstrate that the durability of a major resistance gene depends on the plant genetic background but the genetic factors involved are still unknown. Using the pepper (Capsicum annuum)/Potato virus Y (PVY)) pathosystem, we aimed to identify genetic factors directly involved in pvr23 resistance breakdown frequency and to compare them with genetic factors affecting quantitative resistance. For QTL mapping experiments, 156 doubled haploid lines carrying the pvr23 resistance allele were tested for pvr23 resistance breakdown frequency, virus accumulation and symptom intensity. Four loci including additive QTLs and epistatic interactions explained together 70% of the variance of pvr23 breakdown frequency. Comparative mapping of the different traits showed that three of the four QTLs controlling the breakdown frequency of the pvr23 allele were also involved in quantitative resistance, indicating that QTLs for quantitative resistance have a pleiotropic effect on the durability of the major resistance gene. This study provides the first mapping of QTLs directly affecting resistance durability and opens the way for sustainable resistance breeding.