The prevalence of various antibiotic-resistant bacteria (ARB) and antibiotic-resistance genes (ARGs) is becoming a global environmental problem. Removal of multiple resistant Escherichia coli strains, carrying a gentamicin resistance gene (aac(3)-II), an amoxicillin-resistance gene (blaTEM-1), tetracycline-resistance genes (tetC and tetW), and integron gene intI1, was investigated using a mesoporous plasma. The experimental results showed that the elimination efficiencies of integron intI1, aac(3)-II, blaTEM-1, tetW, and tetC reached 5.46, 5.71, 5.19, 2.88, and 2.28 log within 10 min of plasma oxidation, respectively. These elimination performances were positively related to the plasma intensity, duration time, and airflow rate. The cell membrane structures were significantly destroyed by the plasma oxidation, accompanied by leakage of ARG-containing DNA. Most of the ARG-containing DNA (more than 96%) was effectively damaged and decomposed to cytosine, guanine, adenine, and thymine. The present research revealed the removal behaviors of ARGs by plasma oxidation and provided an alternative to eliminate ARGs in an aqueous system.