Selective oxidation, a fundamental organic transformation of critical importance, produces value-added products from simple organic molecules. This process is extensively used to incorporate heteroatoms into carbon-based molecules, where high-valent metal salts, hypervalent halogen reagents, and peroxides are widely used as oxidants. Oxidation reactions are extremely challenging because their selectivity is hard to control and/or they form significant quantities of unwanted waste derived from the stoichiometric oxidants. Undoubtedly, the utilization of green oxidants such as molecular oxygen (O2) or internal oxidants provides tunable oxidation abilities and produces no environmentally hazardous byproducts. Thus, synthetic chemists have devoted increasing attention to the utilization of green oxidants to obtain valuable products. Since the first industrial application of noble metal-catalyzed oxidation, i.e., Pd/Cu/O2-mediated Wacker oxidation, precious metal-catalyzed organic reactions have undergone significant development in both the laboratory and industry. However, the high cost and considerable toxicity of precious metals compel chemists to explore the catalytic activities of earth-abundant, first-row transition metals. Copper is abundant, easy to utilize, and relatively insensitive to water and air. Controllable access to Cu(0), Cu(I), Cu(II), and Cu(III) oxidation states ensures that copper can be applied as a tunable and multifunctional catalyst. Copper-catalyzed transformations involve single-electron transfer (SET), two-electron processes (TEPs) and even the cooperation of SET and TEPs. More importantly, in Cu/O2 catalytic systems, ligands, additives, and solvents can tune the oxidation state of copper from Cu(I) to Cu(III). As a result, the development of copper-catalyzed aerobic oxidative reactions is possible and desirable. Progress in these synthetic methods will enable breakthroughs in natural product synthesis, materials science, and bioorganic chemistry. This Account describes our efforts over the last several years to develop copper-catalyzed C-C or C-heteroatom bond formation reactions with oxygen or internal oxidants as the oxidant. We primarily focused on reaction with simple substrates, including cross-couplings, cycloadditions, cyclizations, and condensations. These transformations provide convenient and efficient strategies for constructing multiple bonds, such as C-C/C-O bonds, C-C/C-N bonds, and C-N/C-S bonds, in one pot. Various alkynes, furans, benzofurans, lactones, sulfones, thioethers, and nitrogen-containing heterocyclic compounds were synthesized with high selectivity and atom economy from abundant, commercially available and inexpensive starting materials. These methods were successfully applied to the construction of drug molecules and skeletons of natural products. Additionally, the designed control experiments and serendipitous observations have given us mechanistic insights into copper-catalyzed green oxidation. Uncovering the activity of copper-catalyzed green oxidation involving oxygen and oxime esters has allowed us to extend the scope of those green oxidation reactions. We believe that copper-catalyzed green oxidation transformations can be made even more eco-friendly and economical in the synthesis of valuable compounds.