An efficient method has been developed for the enantioselective synthesis of the aflatoxin system with multiple stereocenters via a sequence of organocatalytic Michael–acetalization–reduction–Nef reactions that proceed with high enantioselectivities (90–99% ee). The one-pot reaction sequence provides a facile entry to the aflatoxin system, including dihydroaflatoxin D₂, which includes a formal total synthesis of aflatoxin B₂. The first total synthesis of (−)- and (+)-microminutinin was also achieved via this protocol.