Environmental surface disinfection is a fundamental component of infection prevention and control (IPC) in healthcare settings. Sodium hypochlorite remains widely used owing to its broad-spectrum efficacy, availability, and low cost. Concerns regarding occupational health risks associated with chlorine spraying have led public health authorities to revise existing guidance. The World Health Organization currently recommends wiping as the preferred chlorine-based surface disinfection method. This policy revision was based on very low certainty evidence, and quantitative data directly comparing exposure risks between methods remain limited. This study quantified and compared occupational exposure to chlorine gas (Cl2) and ultrafine particles (UFPs) generated during surface disinfection with sodium hypochlorite applied by spraying versus wiping and assessed the influence of task duration and environmental conditions on cumulative exposure. Under controlled conditions, UFP and Cl2 emission factors (EFs) were measured, and a randomized crossover simulation was conducted to determine disinfection duration per method in a mock clinical room. A well-mixed room model estimated airborne concentrations and inhaled doses across 0.1 to 12 air changes per hour (ACH), including under high temperature, with organic load and soap-with-ammonia interaction. Mean UFP EFs were comparable between methods (spraying 3.1 × 108 and wiping 1.95 × 108 particles·min−1·m−2), while Cl2 concentrations remained below detection limits. Spraying was significantly faster (9.4 ± 3.0 vs. 25.0 ± 7.1 min; p < 0.001) and consistently resulted in lower cumulative exposure: at 0.2 ACH, wiping produced a 4.3-fold higher inhaled UFP dose. Across the 0.1 to 12 ACH range, spraying reduced the inhaled dose by 50 to 75% (p < 0.001). Although environmental factors exerted a stronger influence on absolute exposures, spraying consistently yielded lower Cl2 and UFP concentrations and inhaled doses. These findings indicate that cumulative inhalation exposure is driven primarily by environmental conditions, task duration, and ventilation, rather than the application method’s intrinsic emission rate. Spraying shortened procedures consistently and reduced inhaled doses relative to wiping, supporting reconsideration of current IPC recommendations to incorporate duration-sensitive exposure-based assessments when selecting disinfection methods.