Abstract: For further understanding the genetic mechanism of cucumber mosaic virus (CMV) resistance in different elite flue-cured tobacco accessions, three inbred lines (Kang88, T.T.8, and FC8) with high resistance to CMV were separately used as paternal parent to construct three F₂ populations, while a susceptible inbred line (C151) as the common maternal parent. The disease resistance level was evaluated by the method of mechanical inoculation at seedling stage in greenhouse, and the inheritance was studied with major gene plus polygene mixed genetic model in multiple generations (P₁, P₂, F₁, and F₂) from three crosses between the three resistant lines and a susceptible line. The results showed that the resistance in both Kang88 and T.T.8 were controlled by two additive-dominance-epistatic major genes and plus-dominant multiple genes (E1 model), and the heritabilities of major genes were 91.91% and 68.50%, respectively. The inheritance of FC8 was fitted by the two additive-dominance-epistatic major genes mixed model (B1 model), and the heritability of major genes was 76.43%. Because of the high heritability of the major genes in all three resistant lines mentioned above, the selection of resistant plant could be carried out at early stage. The epistatic effects of major genes, as well as the additive and dominance effects of polygene in both Kang88 and T.T.8, played a positive role in enhancing resistance level, which could be utilized in breeding. The two major genes in FC8 showed significant dominant effects, and were suitable for heterosis utilization.