Agricultural non-point source pollution has received widespread attention in recent years due to its characteristics of dispersion, uncertainty, extensiveness and high difficulty in control. Among them, components such as fertilizers, heavy metals and herbicides constitute complex inorganic–organic composite pollution, which poses great threat to agricultural water ecosystem. Therefore, in this study, phosphate (P), lead (Pb) and atrazine (ATZ) as typical pollutants from agricultural non-point sources were investigated to remove collaboratively by constructing an environmentally friendly zero-valent iron (ZVI)-activated calcium peroxide (CaO2) system. At unadjusted initial pH 2.86, with the mass ratio of ZVI/CaO2 1:1, the removal efficiencies of P, Pb and ATZ were 95.3%, 97.4%, and virtually 100%, respectively. The main active species in the ZVI/CaO2 system was identified as hydroxyl radicals (·OH) by quenching experiment, electron spin resonance test and probe experiment. The characterization results showed that P was mainly precipitated in the form of Ca-P and Fe-P species. Pb was mainly adsorbed and reduced by ZVI and precipitated in solution. ATZ was mainly degraded into ten by-products, and the overall toxicity showed a decrease. The influence of pH on the removal efficiencies of pollutants was reflected in the fact that high pH promoted the removal of P and Pb but inhibited the degradation of ATZ. The ZVI/CaO2 system performed well under the influence of humic acid and typical anions. Therefore, this work provides a promising technology for the organic–inorganic co-polluted water treatment.