The reductive lactonization strategy provides an efficient access to stereoenriched polycyclic γ-lactones. However, it is still a formidable challenge to develop an efficient and versatile protocol with excellent levels of diastereocontrol. Herein we provide a highly diastereoselective and efficient route to diastereopure bi- and polycyclic γ-lactones, by means of an iridium-catalyzed hy-dride transfer strategy. This method features high levels of stereocontrol, broad substrate scope, and high catalyst efficiency (S/C = up to 5000). Mechanistic studies suggested that the iridium hydride formation be the rate-determining step, and that the hydride transfer step be the diastereo-determining step. The large steric hindrance of the iridium hydride species and intramolecular hydro-gen bonding are critically key to the diastereocontrol of the hydride transfer process. From the perspectives of configurational anal-ysis and Duniz angles of attack, the nature of diastereocontrol is well rationalized. A more general empirical rule based on facial se-lectivity analysis for explaining and predicting the stereochemistry is also proposed.