Transition-metal dichalcogenide WSe 2 has attracted increasing interest due to its large thermopower (S), low-cost, and environment-friendly constituents. However, its thermoelectric figure of merit, ZT, of WSe 2 is limited due to its large lattice thermal conductivity (κ L ) and low electrical conductivity. In view of WSe 2 and MoS 2 having the same crystal structure, here we designed and prepared Nb-doped quarternary mixed crystal (MC) Nb 0.05 W 0.95−x Mo x (Se 1−x S x ) 2 (0 ≤ x ≤ 0.095). The results indicate that the κ L of the MC can reach as low as 0.12 W m K −1 at 850 K, being 93% smaller than that of WSe 2 . Our analysis reveals that its low κ L originates chiefly from intense scattering of both highfrequency phonons from point defects (mainly alloying elements) and mid/low-frequency phonons from MoS 2 inclusions residual within MC. In addition, the alloying of WSe 2 with MoS 2 causes a 5-fold increase in cation vacancies (V W ‴′), leading to a large increase in hole concentration and electrical conductivity, which gives rise to a ∼7.5 times increase in power factor (reaching 4.2 μ W cm −1 K −2 at 850 K). As a result, a record high ZT max = 0.63 is achieved at 850 K for the MC sample with x = 0.076, which is 20 times larger than that of WSe 2 , demonstrating that MC Nb 0.05 W 0.95−x Mo x (Se 1−x S x ) 2 is a promising thermoelectric material.