The first catalytic asymmetric desymmetrization of azetidines is disclosed. Despite the low propensity of azetidine ring-opening and challenging stereocontrol, smooth intermolecular reactions were realized with both excellent efficiency and enantioselectivity. These were enabled by suitable combination of catalyst, nucleophile, protective group, and reaction conditions. The highly enantioenriched densely-functionalized products are versatile precursors to other useful chiral molecules. Mechanistic studies, including DFT calculations, revealed that only one catalyst molecule is involved in the key transition state, though both reactants can be activated. Furthermore, the Curtin-Hammett principle dictates the reaction proceeds via amide nitrogen activation.