Direct functionalization of methane selectively to value-added chemicals is still one of the main challenges in modern science. Acetic acid is an important industrial chemical produced nowadays by expensive and environmentally unfriendly carbonylation of methanol using homogeneous catalysts. Here, we report a new photocatalytic reaction route to synthesize acetic acid from CH₄ and CO at room temperature using water as the sole external oxygen source. The optimized photocatalyst consists of a TiO₂ support and ammonium phosphotungstic polyoxometalate (NPW) clusters anchored with isolated Pt single atoms (Pt₁). It enables a stable synthesis of 5.7 mmol·L^–1 acetic acid solution in 60 h with the selectivity over 90% and 66% to acetic acid on liquid-phase and carbon basis, respectively, with the production of 99 mol of acetic acid per mol of Pt. Combined isotopic and in situ spectroscopy investigation suggests that synthesis of acetic acid proceeds via a photocatalytic oxidative carbonylation of methane over the Pt₁ sites, with the methane activation facilitated by water-derived hydroxyl radicals.