Developing high-performance thermoelectric materials is one of the crucial aspects for direct thermal-to-electric energy conversion. Herein, atomic scale point defect engineering is introduced as a new strategy to simultaneously optimize the electrical properties and lattice thermal conductivity of thermoelectric materials, and (Bi,Sb)(2)(Te,Se)(3) thermoelectric solid solutions are selected as a paradigm to demonstrate the applicability of this new approach. Intrinsic point defects play an important role in enhancing the thermoelectric properties. Antisite defects and donor-like effects are engineered in this system by tuning the formation energy of point defects and hot deformation. As a result, a record value of the figure of merit ZT of approximate to 1.2 at 445 K is obtained for n-type polycrystalline Bi2Te2.3Se0.7 alloys, and a high ZT value of approximate to 1.3 at 380 K is achieved for p-type polycrystalline Bi-0.3 Sb1.7Te3 alloys, both values being higher than those of commercial zone-melted ingots. These results demonstrate the promise of point defect engineering as a new strategy to optimize thermoelectric properties.