The joint segregation analysis method of mixed major gene plus polygene genetic model was used to study the inheritance of leaf number and leaf area in flue-cured tobacco. Six generations (P1, P2, F1, B1, B2, and F2) from the crosses between Wanye with less leaves and small leaf area as the maternal parent and Coker319 with more leaves and large leaf area as the paternal parent were investigated. It was found that leaf number and leaf area in flue-cured tobacco appeared to be a quantitative trait and their inheritances fit to a mixed genetic model of two major genes with additive-dominant-epistatic effects plus polygenes with additive-dominant-epistatic effects (the E0 model). Leaf number was mainly controlled by the additive effect and the epistatic effect of dominance × dominance. The additive, dominant and epistatic effects of leaf area was all important with the epistatic effect > the additive effect > the dominance effect. Heritabilities of the major genes were estimated to be 36.91% and 2.13% in B1, 51.60%, and 50.92% in B2 and 42.63% and 30.32% in F2. Heritabilities of the polygenes were estimated to be 31.00% and 19.53% in B1, 16.84% and 13.26% in B2, and 42.08% and 12.18% in F2. Because of their higher heritability of the major gene, the selection of leaf number and leaf area could be taken in early generations.