Oxidation of aromatic rings and its alkyl substituents are often competing initial steps of organic pollutant transformation. The use of compound-specific isotope analysis (CSIA) to distinguish between these two pathways quantitatively, however, can be hampered by large H isotope fractionation that precludes calculation of apparent (2)H-kinetic isotope effects (KIE) as well as the process identification in multi-element isotope fractionation analysis. Here, we investigated the C and H isotope fractionation associated with the transformation of toluene, nitrobenzene, and four substituted nitrotoluenes by permanganate, MnO4(-), to propose a refined evaluation procedure for the quantitative distinction of CH3-group oxidation and dioxygenation. On the basis of batch experiments, an isotopomer-specific kinetic model, and density functional theory (DFT) calculations, we successfully derived the large apparent (2)H-KIE of 4.033 ± 0.20 for the CH3-group oxidation of toluene from H isotope fractionation exceeding >1300‰ as well as the corresponding (13)C-KIE (1.0324 ± 0.0011). Experiment and theory also agreed well for the dioxygenation of nitrobenzene, which was associated with (2)H- and (13)C-KIEs of 0.9410 ± 0.0030 (0.9228 obtained by DFT) and 1.0289 ± 0.0003 (1.025). Consistent branching ratios for the competing CH3-group oxidation and dioxygenation of nitrotoluenes by MnO4(-) were obtained from the combined modeling of concentration as well as C and H isotope signature trends. Our approach offers improved estimates for the identification of contaminant microbial and abiotic oxidation pathways by CSIA.