Uranium dioxide (UO2), the primary fuel for commercial nuclear reactors, incorporates excess oxygen forming a series of hyperstoichiometric oxides. Thin layers of these oxides, such as UO2.12, form readily on the fuel surface and influence its properties, performance, and potentially geologic disposal. This work reports a rapid and straightforward combustion process in uranyl nitrate-glycine-water solutions to prepare UO2.12 nanomaterials and thin films. We also report on the investigation of the structural changes induced in the material by irradiation. Despite the simple processing aspects, the combustion synthesis of UO2.12 has a sophisticated chemical mechanism involving several exothermic steps. Raman spectroscopy and single-crystal X-ray diffraction (XRD) measurements reveal the formation of a complex compound containing the uranyl moiety, glycine, H2O, and NO3- groups in reactive solutions and dried combustion precursors. Combustion diagnostic methods, gas-phase mass spectroscopy, differential scanning calorimetry (DSC), and extracted activation energies from DSC measurements show that the rate-limiting step of the process is the reaction of ammonia with nitrogen oxides formed from the decomposition of glycine and uranyl nitrate, respectively. However, the exothermic decomposition of the complex compound determines the maximum temperature of the process. In situ transmission electron microscopy (TEM) imaging and electron diffraction measurements show that the decomposition of the complex compound directly produces UO2. The incorporation of oxygen at the cooling stage of the combustion process is responsible for the formation of UO2.12. Spin coating of the solutions and brief annealing at 670 K allow the deposition of uniform films of UO2.12 with thicknesses up to 300 nm on an aluminum substrate. Irradiation of films with Ar2+ ions (1.7 MeV energy, a fluence of up to 1 × 1017 ions/cm2) shows unusual defect-simulated grain growth and enhanced chemical mixing of UO2.12 with the substrate due to the high uranium ion diffusion in films. The method described in this work allows the preparation of actinide oxide targets for fundamental nuclear science research and studies associated with stockpile stewardship.