Background Work-related injuries (WRIs) are a major occupational health issue among healthcare workers (HCWs) worldwide. HCWs face numerous daily hazards including needlestick injuries, chemical exposures, ergonomic strains, and psychological stressors crucial for their health and healthcare system functionality.In Makkah, Saudi Arabia, healthcare infrastructure advances raise concerns about work-related injuries among HCWs. This study in Makkah hospitals aims to identify, understand, and manage WRIs for improved occupational health guidelines and strategies. Methods This descriptive cross-sectional study on HCWs was conducted at Makkah hospitals using an electronic questionnaire that investigated the demographics, work-related injuries, and occupational hazards. The data collected from the retrieved questionnaires were analyzed using the IBM SPSS Statistics for Windows, Version 26.0 (Released 2019; IBM Corp., Armonk, New York, United States). Results Among 379 enrolled HCWs, 172 (49.3%) were physicians and 89 (19.8%) were nurses; 304 (80.2%) of the total participants knew about occupational safety. The total incidence of WRIs was 67.8%. WRIs were significantly associated with age (P˂0.001), gender (P=0.02), educational level (P˂0.001), profession (P˂0.001), working hours (P˂0.001), and shift time (P˂0.001). Conclusion WRIs were highly prevalent among HCWs with varying rates based on the type of injury and the frequency of injury. WRIs were associated with various factors including age, gender, education, profession, working house, and shift time of the participants.