The growth and attachment of highly resistant biofilms on/to polymer-based surfaces, including reusable medical devices is a significant health concern in infection control. The increasing prevalence of the multidrug-resistant yeast, Candida auris, has recently garnered immense interest as a contributor to healthcare-associated infections. In this study, we investigate the potential of disinfection processes (ozone, UVC, and ozone + UVC) to inactivate C. auris biofilms (NCPF 8971), grown on polystyrene surfaces. A bespoke decontamination chamber is used to expose the substrate for 20–60 mins, corresponding to ozone doses between 1000 and 3000 ppm.min and UVC doses between 2864 and 11,592 mJ/cm2, respectively. The performance of these 3 treatment methods against the biofilms and vegetative/planktonic cells of the organism is comparatively evaluated. While complete inactivation (> 8 log10 reduction, CFU/mL) of the vegetative cells is observed within 40 mins by all methods, the biofilms proved considerably difficult to inactivate. Only 3.3 log10 reduction was achieved using ozone for 40 min, whereas 7.2 log10 reduction was obtained using UVC for 40 min. A hybrid application of ozone and UVC improved the decontamination efficacy compared to their independent applications (i.e., ozone only and UVC only). Scanning electron microscopy results yielded new insights into the inactivation mechanisms; thus providing the needed foundation for newer developments in oxidation-based processes for biofilm mitigation and control.