The widespread use of synthetic dyes has led to the release of substantial amounts of dye-contaminated wastewater, posing significant environmental and health concerns. This study focuses on the use of anodic and electrochemically activated persulfate oxidation for the degradation of organic contaminants. Specifically, the structural variations of nine dyes in the indigoid and azo families, and their impact on the efficiency of electrochemical oxidation were analyzed. An in situ continuous monitoring apparatus with a UV-visible detector was employed to collect data in real-time. The electrochemically activated persulfate system demonstrated higher efficiency compared to the anodic oxidation approach. In both systems the efficiency of decolorization was highly dependent on the structure of the pollutant. Electron-withdrawing substituents in direct conjugation with the chromophore, bulky auxochromes, and extended aromatic systems significantly decreased the decolorization efficiency. Conversely, changing the location of electron-withdrawing groups and adding electron-donating substituents increased the decolorization efficiency, even overcoming the detrimental effects of bulky groups and extended conjugation. This type of systematic structural comparison study is essential for highlighting the interconnected nature of pollutant structure and degradation speed so that efficient electrochemical oxidation systems can be designed for the treatment of genuine wastewater effluent containing more than one pollutant.