Revealing the nature of intrinsic defects that act as charge-carrier trapping centers for persistent luminescence (PersL) in inorganic phosphors remains a crucial challenge from an experimental perspective. It was recently reported that Bi3+-doped LiREGeO4 (RE = Sc, Y, Lu) compounds displayed strong ultraviolet-A PersL at ∼360 nm with a duration of tens of hours at room temperature. However, the mechanistic origin of the PersL remains to be unveiled. Herein, we carried out a systematic study on optical transitions, formation energies, and charge-transition levels of dopants and intrinsic point defects in these compounds using hybrid density functional theory calculations. The results show that the efficient charging by 254 nm is due to the D-band transition of Bi3+ and hence the charge carriers pertinent to PersL are electrons originating from the dopants which are involved in the trapping and detrapping processes. The main electron-trapping centers are antisite defects GeLi0, interstitial defects Lii0, and dopants Bi2+, with the former one responsible for the strong PersL and the latter two for its long-time duration. These findings are further confirmed by comparison with calculated results for isostructural NaLuGeO4 and LiLuSiO4, based on which the roles of Li and Ge elements in forming intrinsic defects with appropriate trap depths for PersL are clarified. Our results not only assist in the understanding of experimental observations but also provide a theoretical basis for the rational design of novel PersL phosphors containing lithium and germanium in the host compound.