Work-related musculoskeletal disorder (WRMSDs) affects primarily muscles, tendons, joints, intervertebral discs, peripheral nerves, and the vascular system. WRMSDs are a worldwide issue and are experienced in both developed countries and industrially developing countries (IDCs). The prevalence of WRMSDs and their risk factors are not well known among hotel housekeepers in Kenya. Therefore, this study aimed to establish the annual prevalence of work-related musculoskeletal disorders among housekeepers in selected hotels in Mombasa County. The study also sought to assess the common body parts affected by pain as well as the WRMD risk factors associated with these body parts among housekeepers at selected hotels in Mombasa County. The study employed a cross-sectional approach. The sample size of 276 study participants’ housekeepers was obtained by considering housekeepers’ availability at the time of study at 18 purposefully selected hotels. Data collection was done through standardized questionnaires. Qualitative and quantitative methods were used for data analysis. Quantitative data was coded and entered into the Statistical Package for Social Sciences (SPSS 23) for analysis. Descriptive and inferential statistical analyses were utilized to analyze the quantitative data collected from the structured questionnaires. To establish the link between variables, descriptive statistical analysis, including frequencies and percentages, and inferential statistical analysis, including the Chi-square test and linear regression, were utilized, with findings displayed in frequency tables, bar graphs, and pie charts. On the other hand, the qualitative analysis utilized thematic analysis, with findings presented in narrations. WRMDs were found to be prevalent in 91.7% of hotel housekeepers in Mombasa County. The most widely reported WRMD by housekeepers was lower back pain. The study cohort also reported leg, neck, and shoulder joint and muscle pains as a result of carrying, lifting, pulling, or pushing heavy objects weighing more than 20 kilograms. Hotels ought to identify the common WRMDs among housekeepers and determine specific risk factors associated with these pains. The study's key recommendations are for hotels to evaluate their labor practices to mitigate understaffing, invest in the mechanization of equipment to ensure that staff have reasonable working hours per day with adequate breaks in between chores, and take reasonable leave. Implementing health and safety standards is crucial, with an emphasis on good posture and techniques while performing tasks. The study recommends strengthening labor regulations by raising awareness and sensitizing labor unions and health committees on musculoskeletal disorders and preventing undue work-related injuries among hotel housekeepers.