Compromise between the electrical conductivity and Seebeck coefficient limits the efficiency of chemical doping in the thermoelectric research. An alternative strategy, involving the control of a local crystal structure, is demonstrated to improve the thermoelectric performance in the RE2SbO2 system. The RE2SbO2 phases, adopting a disordered anti-ThCr2Si2-type structure (I4/mmm), were prepared for RE = La, Nd, Sm, Gd, Ho, and Er. By traversing the rare earth series, the lattice parameters of the RE2SbO2 phases are gradually reduced, thus increasing chemical pressure on the Sb environment. As the Sb displacements are perturbed, different charge carrier activation mechanisms dominate the transport properties of these compounds. As a result, the electrical conductivity and Seebeck coefficient are improved simultaneously, while the number of charge carriers in the series remains constant.