Direct photocatalytic conversion of methane to value-added C(1) oxygenate with O(2) is of great interest but presents a significant challenge in achieving highly selective product formation. Herein, a general strategy for the construction of copper single-atom catalysts with a well-defined coordination microenvironment is developed on the basis of metal-organic framework for selective photo-oxidation of CH(4) to HCHO. We propose the directional activation of O(2) on the mono-copper site breaks the original equilibrium and tilts the balance of radical formation almost completely toward •OOH. The synchronously generated •OOH and •CH(3) radicals rapidly combine to form HCHO while inhibiting competing reactions, thus resulting in ultra-highly selective HCHO production (nearly 100%) with a time yield of 2.75 mmol g(cat)(-1) h(-1). This work highlights the potential of rationally designing reaction sites to manipulate reaction pathways and achieve selective CH(4) photo-oxidation, and could guide the further design of high-performance single-atom catalysts to meet future demand.