Degradation kinetics of antibiotic resistance genes (ARGs) by free available chlorine (FAC), ozone (O3), and UV254 light (UV) were investigated in phosphate buffered solutions at pH 7 using a chromosomal ARG (mecA) of methicillin-resistant Staphylococcus aureus (MRSA). For FAC, the degradation rates of extracellular mecA (extra-mecA) were accelerated with increasing FAC exposure, which could be explained by a two-step FAC reaction model. The degradation of extra-mecA by O3 followed second-order reaction kinetics. The degradation of extra-mecA by UV exhibited tailing kinetics, which could be described by a newly proposed kinetic model considering cyclobutane pyrimidine dimer (CPD) formation, its photoreversal, and irreversible (6-4) photoproduct formation. Measured rate constants for extra-mecA increased linearly with amplicon length for FAC and O3, or with number of intrastrand pyrimidine doublets for UV, which enabled prediction of degradation rate constants of extra-mecA amplicons based on sequence length and/or composition. In comparison to those of extra-mecA, the observed degradation rates of intracellular mecA (intra-mecA) were faster for FAC and O3 at low oxidant exposures but significantly slower at high exposures for FAC and UV. Differences in observed extra- and intracellular kinetics could be due to decreased DNA recovery efficiency and/or the presence of MRSA aggregates protected from disinfectants.