An experimental design methodology has been drawn regarding the model contaminant 2,4-dichlorophenol (2,4-DCP) oxidation using Fenton's reagent. This multivariable and multilevel approach allowed us to investigate the effects between the experimental variables (temperature and iron(II) and hydrogen peroxide concentrations) in the process performance, with the minimum number of experiments. Response factors considered were 2,4-DCP degradation after 5, 10, and 20 min of reaction time, for an initial 2,4-DCP concentration of 100 mg/L. This approach provided statistically significant models, which allowed process optimization. It was found that, within the range studied, the ferrous concentration has a positive effect on the oxidation performance. However, for the peroxide load, and particularly for temperature, an optimal value exists that must be taken into account in order to obtain the best results. Besides, the optimal conditions depend on the response considered, with it being advisable to use less-aggressive conditions if responses are taken at longer reaction times. Finally, the kinetic model proposed was useful for predicting the evolution of the 2,4-DCP concentration within the batch reactor over time. Moreover, this kinetic analysis also allowed us to establish the reaction rate for 2,4-DCP degradation.