Bimolecular reactions of uranium oxide molecular anions with methanol have been studied experimentally, by Fourier transform ion cyclotron resonance mass spectrometry, and computationally, by density functional theory (DFT). The primary goals were to provide fundamental insights into mechanistic and structural details of model reactions of uranium oxides with organics, and to examine the validity of theoretical modeling of these types of reactions. The ions UO3-, UO4-, and UO4H-each reacted with methanol to give a singular product; the primary products each exhibited sequential reactions with two additional methanol molecules to again give singular products. The observed reactions were elimination of water, formaldehyde, or hydrogen, and in one case addition of a methanol molecule. The potential energy profiles were computed for each reaction, and isotopic labeling experiments were performed to probe the validity of the computed mechanisms and structures-in each case where the experiments could be compared with the theory there was concurrence, clearly establishing the efficacy of the employed DFT methodologies for these and related reaction systems. The OFT results were furthermore in accord with the surprisingly inert nature of UO2-. The results provide a basis to understand mechanisms of key reactions of uranium oxides with organics, and a foundation to extend DFT methodologies to more complex actinide systems which are not amenable to such direct experimental studies.