A visible-light-induced, synergistic excited-state cobaloxime catalysis system has been developed to perform the dehydrogenative C(sp²)–H phosphinoylation of various undirected bioactive molecules accompanied by H₂ evolution. This protocol is conducted under oxidant-free conditions and is featured with high regioselectivity as well as a broad substrate scope (more than 60 examples; yields up to 90%). Notably, the successful achievement for the C(sp³)–H phosphinoylation of tetrahydroisoquinolines and the late-stage phosphinoylation of several marketed drugs further proves the potential synthetic utility of this approach. Mechanistic studies indicate that this transformation may proceed through a radical pathway.