Direct treatment of water purification membranes with strong oxidative chemicals, such as ozone and chlorine, is a promising avenue to prevent fouling and improve the water treatment performance. In this work, we investigate the oxidation resistance of hydrophobic polymers commonly used in membrane distillation by probing the impact of ozone and chlorine exposure on the membrane structure, chemistry, and desalination performance. To probe oxidative behavior, polytetrafluoroethylene (PTFE), polyvinylidene fluoride (PVDF), and polypropylene (PP) membranes were exposed to sodium hypochlorite (10,000 ppm, pH 4) and ozone (15 ppm, pH 7) solutions for up to 72 and 3 h, respectively. We then characterized the membrane samples using Fourier transform infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), water contact angle measurements, and desalination performance testing. Our results indicate that PTFE membranes show no chemical, structural, or desalination performance changes after exposure to the highest doses of chlorine and ozone, with only minor decreases in the water contact angle (less than 15%) after exposure to oxidants. PVDF also showed no observable changes in structure or performance, although XPS analysis indicated possible defluorination of the surface after oxidant exposure. PP membranes showed the most severe degradation, with surface cracking, chemical changes, and complete failure in desalination testing after exposure to 10,000 ppm chlorine for 1 h or 15 ppm ozone for 30 min. Measurements of salt rejection and water flux of the pristine and oxidized membranes showed greater than 99.9% rejection and minimal changes in water flux regardless of oxidant or exposure length, except in the case of PP which showed failure during testing. Our results provide insights into the degradation behavior of hydrophobic polymer membranes and demonstrate the promise of using PTFE and PVDF membranes combined with strong oxidants in water treatment.