BACKGROUND: Work-related stress is described as a physiological and psychological reaction to the harmful aspects of workplace content. Current evidence indicates that the world of education is a highly stressful occupation. However, in academicians in sub-Saharan African countries, such as Ethiopia,the prevalence and contributing factors are not well studied. This study was, therefore, aimed at filling this gap.METHODS: A cross-sectional study was conducted from March to April 2018. Stratified sampling technique was used to select 535 study participants. To measure work-related stress, we used the pre-tested and structured self-administered University and College Union stress questionnaire. Finally, a significant association was established at p< 0.05 and adjusted odds ratio (AOR) with 95% confidence intervals (CI) in the multivariable model.RESULTS: The overall prevalence of work-related stress in 12 months was 60.4% [95% CI (57.4, 63.5%)].The multivariable logistic regression analysis showed that smoking cigarette (AOR:2.84, 95% CI (1.25, 6.50), high job demand (AOR: 3.27, 95% CI(2.05, 5.21), low job control (AOR:2.25, 95% CI (1.21, 4.20) and age < 28 (AOR:0.25, 95% CI (0.10, 0.63) were the factors associated with work-related stress.CONCLUSION: The prevalence of work-related stress was high. Furthermore, higher emphasis required on job demand, job control, and cigarette smoking to ease the burden of work-related stress factors. This research, therefore, recommended that other causes of WRS, such as working conditions and further large-scale study, be considered for future research.