Copper phosphate nanostructures were investigated as catalysts for the direct oxidation of methane (CH₄) to formaldehyde (HCHO) using molecular oxygen (O₂) as the sole oxidant. The study evaluated the effectiveness of various copper phosphate catalysts, including four crystalline copper phosphates (Cu₂P₂O₇, Cu₃(PO₄)₂, Cu₂(P₄O₁₂), and Cu₄O(PO₄)₂), synthesized from Cu(OAc)₂·H₂O and (NH₄)₂HPO₄. The Cu/P molar ratio significantly influenced the oxidation of CH₄, with Cu₂P₂O₇ showing the highest HCHO yield among the investigated catalysts. The catalytic activity of Cu₂P₂O₇ was enhanced by using Cu(NO₃)₂·3H₂O as the copper source, which allowed for better surface nanostructure control. Mechanistic studies, including catalyst effects, kinetics, isotope-labeling, and pulse reaction experiments, revealed that surface lattice oxygen species of Cu₂P₂O₇ likely react with CH₄ to produce HCHO as the primary product. Additionally, surface redox-active Lewis acidic Cu²⁺ sites and weakly basic phosphate units on Cu₂P₂O₇ play important roles in C–H activation and the suppression of overoxidation to CO₂. Density functional theory calculations showed that the vacancy formation energies of oxygen sites in β-Cu₂P₂O₇, formed by the phase transition of α-Cu₂P₂O₇ under catalytic conditions, were lower than those in α-Cu₂P₂O₇, contributing to the high catalytic performance and durability of Cu₂P₂O₇ for CH₄ oxidation. The study demonstrated that Cu₂P₂O₇ is an effective catalyst for the direct oxidation of CH₄ to HCHO, with high selectivity and activity. The results highlight the importance of surface nanostructures and the interplay between redox-active and acid-base-active sites in the catalytic performance of copper phosphates. The findings suggest that further investigation into the structural and operational properties of Cu₂P₂O₇ under catalytic conditions is needed to fully understand the active oxygen species involved in the reaction.Copper phosphate nanostructures were investigated as catalysts for the direct oxidation of methane (CH₄) to formaldehyde (HCHO) using molecular oxygen (O₂) as the sole oxidant. The study evaluated the effectiveness of various copper phosphate catalysts, including four crystalline copper phosphates (Cu₂P₂O₇, Cu₃(PO₄)₂, Cu₂(P₄O₁₂), and Cu₄O(PO₄)₂), synthesized from Cu(OAc)₂·H₂O and (NH₄)₂HPO₄. The Cu/P molar ratio significantly influenced the oxidation of CH₄, with Cu₂P₂O₇ showing the highest HCHO yield among the investigated catalysts. The catalytic activity of Cu₂P₂O₇ was enhanced by using Cu(NO₃)₂·3H₂O as the copper source, which allowed for better surface nanostructure control. Mechanistic studies, including catalyst effects, kinetics, isotope-labeling, and pulse reaction experiments, revealed that surface lattice oxygen species of Cu₂P₂O₇ likely react with CH₄ to produce HCHO as the primary product. Additionally, surface redox-active Lewis acidic Cu²⁺ sites and weakly basic phosphate units on Cu₂P₂O₇ play important roles in C–H activation and the suppression of overoxidation to CO₂. Density functional theory calculations showed that the vacancy formation energies of oxygen sites in β-Cu₂P₂O₇, formed by the phase transition of α-Cu₂P₂O₇ under catalytic conditions, were lower than those in α-Cu₂P₂O₇, contributing to the high catalytic performance and durability of Cu₂P₂O₇ for CH₄ oxidation. The study demonstrated that Cu₂P₂O₇ is an effective catalyst for the direct oxidation of CH₄ to HCHO, with high selectivity and activity. The results highlight the importance of surface nanostructures and the interplay between redox-active and acid-base-active sites in the catalytic performance of copper phosphates. The findings suggest that further investigation into the structural and operational properties of Cu₂P₂O₇ under catalytic conditions is needed to fully understand the active oxygen species involved in the reaction.