Silver-mediated C(sp3)–H functionalization and 6-endo-dig oxo-cyclization of conjugated β-alkynyl ketones have been established under oxidative conditions. The reaction leads to the concise formation of a wide range of isochromenes via C(sp3)–H bond-breaking and radical addition steps. Dual and monofunctional isochromene products were selectively controlled by using either electron-rich or electron-deficient radical sources.