The presence of organic sulfides in fuels has become a significant contributing factor to the formation of haze weather. The desulfurization of fuels has become a frontier scientific topic demanding urgent solutions. Research shows that acidic deep eutectic solvents (DESs) can provide a new route for the deep oxidation/extraction desulfurization of fuels because of their cheap and easily obtained raw materials, higher desulfurization efficiencies, environmentally friendly properties and simple synthetic procedures. Through smart design, a series of acidic DESs with different acidities were synthesized. These acidic DESs were applied for the successful deep oxidation/extraction desulfurization of model and real fuels. Results show that the acidity of deep eutectic solvents is the main factor that determines the oxidation/extraction process. The desulfurization capability has a positive correlation with the acidity of DESs, that is, the stronger a DES’s acidity, the higher the desulfurization efficiencies achieved. Under optimal conditions, the desulfurization efficiencies of DESs choline chloride/p-toluenesulfonic acid (ChCl/p-TsOH) and tetrabutylammonium chloride/p-toluenesulfonic acid (TBAC/p-TsOH) can reach up to 99.99%. For the real fuel, the desulfurization efficiency can reach up to 97.25% and 95.90%, for (ChCl/p-TsOH) and (TBAC/p-TsOH) respectively. Finally, the final product was characterized and the oxidation/extraction mechanism was also investigated and the possible desulfurization route was proposed. The above study will provide new technology for the desulfurization of fuels.