A facile incorporation of a privileged sulfide, a naphthofuran framework, and a perfluoroalkyl moiety in one molecule was successfully accomplished through tandem defluorinative sulfenylation of α-perfluoroalkyl ketones with a sulfur source. The reaction presumably proceeds via a sequence involving defluorination, reductive sulfenylation, autoaromatization, and annulation, accompanied by the simultaneous cleavage of four C(sp³)–F bonds and the formation of new C–S and C–O bonds.