A chemoselective synthesis of fused novel tricyclic motifs via a facile domino intramolecular cyclization is presented. The strategy enables the formation of dual C-C bond via intramolecular Friedel-Crafts alkylation followed by acylation to accomplish fused tricyclic ketones. Significantly, these fused tricyclic compounds are ubiquitous and constitute major structural cores of natural products. © 2018 American Chemical Society.