Catalytic enantioselective C-C bond forming process through cross-dehydrogenative coupling represents a promising synthetic strategy, but it remains a long-standing challenge in chemistry. Here, we report a formal catalytic enantioselective cross-dehydrogenative coupling of saturated ethers with diverse carboxylic acid derivatives involving an initial oxidative acetal formation, followed by nickel(II)-catalyzed asymmetric alkylation. The one-pot, general, and modular method exhibits wide compatibility of a broad range of saturated ethers not only including prevalent tetrahydrofuran and tetrahydropyran, but also including medium- and large-sized cyclic moieties and acyclic ones with excellent enantioselectivity and functional group tolerance. The application in the rapid preparation of biologically active molecules that are difficult to access with existing methods is also demonstrated.