The electrochemical decolorization of the Reactive Violet 5 azo dye on a boron-doped diamond anode was used as a model process to test a novel definitive screening design (DSD). This method allows a dramatic reduction in the number of experiments needed to investigate those systems characterized by a large number of variables. In this study, the effect of nine quantitative parameters was investigated: initial dye concentration (60–120 mg L −1 ), current density (100–500 A m −2 ), NaCl concentration (5–20 mM), Na 2 SO 4 concentration (35–65 mM), pH (3–11), temperature (20–45 °C), inter-electrode distance (0.5–3.5 cm), stirring rate (250–750 rpm) and electrolysis time (2–8 min). Analysis of DSD data showed that four out of the nine factors (initial dye concentration, current density, pH and electrolysis time) were statistically significant. These factors were retained for process characterization using a subsequent central composite design. Overall, the number of experiments was reduced from over 500 to only 41, thus confirming the validity of the proposed approach as a time-saving and efficient method.