In recent years, a variety of antibiotics in water, such as oxytetracycline (OTC), tetracycline (TC) and norfloxacin, have received increasing attention because they cannot be effectively degraded due to their toxic and recalcitrant performance. Experimental results reveal that Cold Atmospheric Plasma (CAP) show great potential in the field of environmental remediation. However, the degradation pathways and products should be further understood. In this paper, the reaction processes of OTC with four Reactive Oxygen Species (ROS), such as hydroxyl radical, oxygen atom, hydrogen peroxide and ozone, were numerically studied by means of reactive Molecular Dynamic (rMD) simulations coupled with ReaxFF field. In the simulation, the breaking of important chemical bonds (such as C–N, C–O, C–C bond), destruction of functional groups (dimethyl amine, amide, hydroxyl), ring-opening reaction, and formation of low molecules (such as formic acid, formaldehyde, carbon dioxide, and nitric acid) are observed. The generation of non-toxic products that cannot combine with bacterial ribosomes means elimination of biological toxicity of oxytetracycline degradation.