The first asymmetric total synthesis of gymnothespirolignan A is disclosed in 11 steps. The salient feature of the synthesis is construction of the spirocyclic moiety through a bioinspired acid-promoted double cyclization of an acyclic gymnothebutyllignan A-like precursor, which involves a deprotection, hemiketalization, dehydrative oxonium formation, and Friedel-Crafts cyclization cascade transformation. This study provides a general approach to the asymmetric syntheses of novel spirocyclic gymnothelignans.