Racemic total synthesis of the natural product oxacyclododecindione, isolated in 2008 as the first member of the oxacyclododecindione family, is reported. Studies toward this molecule commenced with a biomimetic late-stage C-H oxidation starting from 14-deoxyoxacyclododecindione as a known precursor. This provided insights into the reactivity of the macrolactone class but did not permit the synthesis of the target natural product. Based on these results, a synthetic strategy through intramolecular Friedel-Crafts acylation combined with Barton decarboxylation to introduce the tertiary alcohol, a major challenge in previous synthetic efforts, was envisioned. This resulted in an 11-step racemic total synthesis of (±)-oxacyclododecindione, renowned for its potent anti-inflammatory and antifibrotic activities.