A novel polysulfone–cerium oxide (Psf–ceria) mixed-matrix membrane (MMM) with enhanced γ radiation resistant property was developed. Ceria nanoparticles were synthesized by gel-combustion route and then various concentrations of ceria (0.1–2% of Psf) were incorporated in the polysulfone matrix to synthesize Psf–ceria MMMs. Radiation stability of the synthesized membranes was checked with γ radiation doses of 100, 500, and 1000 kGy. Ceria nanoparticles were characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy, small-angle X-ray scattering (SAXS), transmission electron microscopy, and energy dispersive X-ray spectroscopy techniques. These characterizations confirmed the successful synthesis of pure, crystalline, and 12 nm average size ceria nanoparticles. Psf–ceria MMMs were synthesized by non-solvent-induced phase inversion technique. The effect of radiation on the morphology and topography of membranes was analyzed using scanning electron and atomic force microscopy studies. The physicochemical properties were examined by drop shape analyzer, Fourier transform infrared spectroscopy, gel permeation chromatography, and XRD studies. These analyses confirmed that ceria nanoparticles were uniformly distributed throughout the Psf membrane matrix without any chemical interaction between the ceria and Psf. The internal structure was evaluated by positron annihilation lifetime spectroscopy and SAXS techniques. The mechanical properties were assessed by universal testing machine. The performance of the membranes was analyzed through pure water permeability and solute (poly(ethylene oxide), 100 kDa) rejection studies. Psf–ceria MMMs showed enhanced stability in the performance compared to that of control Psf membrane. The stability of ceria is due to its two oxidation states and its ability to scavenge free radicals by swiping between those two states (Ce⁴⁺ ↔ Ce³⁺). This makes the MMMs radiation resistant, with 0.5–1% loaded Psf–ceria membrane five times enhanced life span in intermediate liquid radioactive effluent environment, compared to control Psf membrane.