The dissemination of antibiotic resistance genes (ARGs) increases risks towards human health and environmental safety. This work investigates the control of ARGs abundance and bacterial community evolution involved in waste activated sludge (WAS) treatment by chemical conditioning and subsequent mesophilic anaerobic digestion (MAD). The different chemical oxidation processes of ferrous iron-activated oxone and hydrogen peroxide (PMS-Fe2+ and H2O2-Fe2+) and thermal-activated oxone (PMS@80 ℃) were investigated, and the ferric chloride (FeCl3) and inactivated oxone (PMS) were compared. PMS@80 ℃ decreased the absolute abundance of most ARGs by 10.6–99.3% and that of total ARGs by 66.3%. Interestingly, oxidation pretreatment increased rather than decreased the relative abundance of most ARGs. MAD with PMS@80 ℃ pretreatment increased the absolute abundance of total ARGs by 51.6%, and other MAD processes decreased it by 8.6–47.4%. PMS-Fe2+ and PMS@80 ℃ negatively inhibited methane production from 98.3 to 81.7 and 94.4 mL/g VSS in MAD. MAD effluent showed high abundance of Arcobacter genus in the range of 8.1–17.4% upon PMS-based pretreatment, possibly related to sulfur oxidation, nitrate reduction, and blaVEB enrichment. The radicals-orientated chemical oxidation can hardly improve the ARGs elimination by MAD due to the extremely high competitive organics in sludge.