Manufacturing enterprises face a strategic challenge in managing risks, as safety concerns can result in huge costs for employee wellbeing and business success. However, there is no clear link between using diverse instruments to assess and measure safety performance and the culture and climate of safety in the workplace, which is likely due to differing perspectives on the topic. This study explores the influence of safety culture and climate on safety performance and on the mediating role of employee engagement in the Ethiopian manufacturing sector. This study was conducted using a quantitative research methodology 368, where three hundred and sixty-eight respondents from five large-scale industrial manufacturing enterprises were selected through purposive sampling. A combination of techniques was used, including structural equation modeling, growth paths, and correlation matrix, and these were performed using the SPSS/AMOS v. 24 software suites. These methods established a causal relationship between safety culture, safety climate, and safety performance. The study’s main finding is that safety culture significantly impacts safety performance, which is followed by safety climate. Additionally, employee engagement played a significant mediating role between safety culture and safety performance, as well as between safety climate and safety performance. Based on these results, policymakers and practitioners in large-scale manufacturing enterprises in Ethiopia should prioritize improving the safety culture and climate of their workplaces to enhance safety performance and overall safety.