The enantioselective total syntheses of (+)-peniciketals A and B, two members of a family of architecturally complex spiroketals, have been achieved. Key synthetic transformations comprise Type I Anion Relay Chemistry (ARC) to construct the benzannulated [6,6]-spiroketal skeleton, a Negishi cross-coupling/olefin cross-metathesis reaction sequence to generate the transenone structure, and a late-stage large fragment union exploiting our recently developed photoisomerization/cydization tactic.