A concise total synthesis of (-)-exiguolide has been completed in an overall 2.8% yield over 20 steps in the longest linear path. The key strategies involve (1) Prins cyclization/homobromination of dienyl alcohol with the B ring-substituted aldehyde, prepared by Prins cyclization/bromination, to construct the A ring with excellent cis-Z stereochemical control and (2) an unusual side chain installation/macrocyclization strategy featuring Sonogashira cross-coupling followed by a ring-closing metathesis reaction to deliver the target.