Shale-oxidant reactions can enhance the permeability of organic-rich shale reservoirs through chemical-induced fracturing. Choosing the best oxidant for this purpose is explored in this study. To compare the effects of chemical-induced fracturing with sodium persulfate (Na2S2O8), sodium hypochlorite (NaClO), and hydrogen peroxide (H2O2) on organic-rich shale, Marcellus shale samples were used to conduct spontaneous imbibition experiments in three oxidants’ aqueous solutions under no confining pressure. The mass loss of samples after oxidant imbibition, the pH change of the oxidants’ aqueous solutions, the bubble density, the morphology of chemical-induced cracks, and the mineral composition alteration before and after Na2S2O8 treatment were analyzed and discussed to evaluate the effects of three oxidants on chemical-induced cracking. Results show that the samples treated by Na2S2O8 had the highest mass loss, while the samples treated by H2O2 had the lowest mass loss. pH change results and bubble density results indicate that the rate of the chemical reactions between Marcellus shale and Na2S2O8 or H2O2 aqueous solutions during the first 24 h was the highest compared to that during the rest of the period. After 24 h, the rate of the chemical reactions decreased and then became flat until the end of the imbibition tests. Pervasive multiscale cracks formed in response to acidic and oxidative dissolutions in Na2S2O8 imbibition tests. Although induced cracks were initiated on the surfaces of the samples treated by NaClO aqueous solutions, Fe(OH)3 precipitates plugged the pores and prevented the cracks from developing into a favorable dimension. XRD results show that the contents of calcite, pyrite, and illite decreased after Na2S2O8 treatment, where calcite had the largest decrease. Gypsum crystallization occurred during Na2S2O8 imbibition. Na2S2O8 was evaluated as the optimal oxidant among three for the initiation and propagation of chemical-induced cracks. Three concentrations (6, 12, and 15 wt %) of Na2S2O8 solutions effectively caused chemical-induced cracks in samples, and the difference in concentrations had no significant difference in the fracturing effect. The synergy of chemical reactions between oxidant shale samples and the generated swelling stress due to crystallization contributes to crack development.