Efficient energy harvesting for applications such as radioisotope thermoelectric generators and heat-recovery systems require novel thermoelectric materials with exceptional performance. This work demonstrates thermoelectric capabilities of n-type MoS2/MoSe2 heterojunctions fabricated by scalable radiofrequency sputtering. These heterostructures demonstrated an outstanding experimental Seebeck coefficient of ~ − 1.1 mV K−1 (ΔT = 40 K), arising from thermally activated carriers with a low activation energy of 32 meV, and estimated thermoelectric figure-of-merit (ZT) values of ~ 1.0. Furthermore, computational calculations within framework of Density Functional Theory corroborate experimental findings allowing to elucidate a crucial role of atomic-scale in determining anisotropic thermoelectric properties.