Rice yellow mottle virus (RYMV) reaches a high virus content in rice, is genetically highly variable and evolves rapidly. Nevertheless, only a small proportion of isolates overcome rymv1-2 rice resistance by mutations in the VPg (viral protein genome-linked). The accumulation rates of wild-type (WT) and resistance-breaking (RB) genotypes of the E- and T-pathotypes of RYMV, with average and low virulence, respectively, were assessed. By quantitative reverse transcriptase-polymerase chain reaction, it was shown that: (i) in resistant plants, both WT genotypes reached a level of 105–107 viral copies per milligram of fresh leaf; (ii) the accumulation of RB genotypes was variable, but was always much higher than the WT, with an RB/WT accumulation ratio of up to 106; (iii) in susceptible plants, the RB genotypes were counter-selected to a similar level. In competition experiments, there was a straightforward exclusion of WT by RB genotypes in resistant hosts. The mutation rate in VPg was more than 1 × 10−3 mutations per site per year. Overall, a steady supply of highly adaptive RB genotypes was expected in resistant plants. However, the use of the few possible mutational pathways to virulence is tightly regulated by pathotype-specific genetic constraints: codon usage, mutational bias and sign epistasis. In addition, genetic drift may restrict the fixation of RB mutants. Altogether, both genetic and demographic constraints contribute to the low ability of RYMV to break rymv1-2 resistance.