Background Workplace stress occurs in all professionals but, in particular, health-care professionals are highly prone to workplace stress. Health-care professionals comprise an important group that can be impacted by workplace stress because of their unique work environment. The study was done to determine the level of workplace stress and its associated factors among health-care professionals in Felege-Hiwot Referral Hospital, Bahir Dar, Northwest Ethiopia. Methods An institutional-based cross-sectional study was conducted among randomly selected health-care professionals in Felege-Hiwot Referral Hospital. Data were collected using a self-administered structured questionnaire by trained data collectors and the supervisor. The collected data were entered into EPI-info version 7 and exported to SPSS version 20 for analysis. Logistic regression was employed to assess the associations between dependent and explanatory variables. Results This study revealed that prevalence of workplace stress was 68.2%. Health professionals who work 50 hours and more per week and in night shift on sometimes base were more likely to develop workplace stress. Conclusion The level of workplace stress among health professionals was found to be high. This was due to long working hours and working in night shift. Identifying the source of workplace stress among health professionals should be a great concern for health service managers and other stakeholders.