Engineering atomic-scale native point defects has become an attractive strategy to improve the performance of thermoelectric materials. Here, we theoretically predict that Ag-Mg antisite defects as shallow acceptors can be more stable than other intrinsic defects under Mg-poor-Ag/Sb-rich conditions. Under more Mg-rich conditions, Ag vacancy dominates the intrinsic defects. The p-type conduction behavior of experimentally synthesized ¿-MgAgSb mainly comes from Ag vacancies and Ag antisites (Ag on Mg sites), which act as shallow acceptors. Ag-Mg antisite defects significantly increase the thermoelectric performance of ¿-MgAgSb by increasing the number of band valleys near the Fermi level. For Li-doped ¿-MgAgSb, under more Mg-rich conditions, Li will substitute on Ag sites rather than on Mg sites and may achieve high thermoelectric performance. A secondary valence band is revealed in ¿-MgAgSb with 14 conducting carrier pockets.