Effective remediation of pesticide-contaminated sites is challenging due to high concentrations of pollutants with complete habitat destruction. Herein, microwave (MW)-activated persulfate (PS) system was proposed for remediation of organochlorine pesticide contaminated soil with atrazine (ATZ) as representation. The results revealed that the MW/PS system could achieve 97.9% of ATZ (50 mg/kg) degradation after treatment of 60 min, superior to that by conventional heat-activated PS. And more excellent degradation performance was identified in relatively higher microwave temperature (80 °C) with appropriate PS concentration (24 mmol/L), MW power (400 W) and water-soil ratio (1:1). Moreover, the MW/PS system possessed high tolerance to co-existing substances including Cl−, HCO3− and H2PO4−, and appropriate organic substance content favored ATZ degradation in soil. Reactive oxygen species consisting of SO4•−, OH•, O2•− and 1O2 contributed to ATZ decomposition, among which O2∙− played a principal role. The ATZ degradation pathway was then elucidated by combination of HPLC/MS spectra and DFT calculations, and ATZ overall toxicity was effectively alleviated in MW/PS system in term of toxicity assessment. Additionally, the MW/PS system presented high-performance degradation on such organochlorine pesticides as trichloro ethylene, tetrachloride, hexachlorobenzene and chlordane, suggesting great potentials of this system for remediation of organochlorine pesticides contaminated sites.