Objective: This study aimed to assess the magnitude of work-related musculoskeletal disorders (WMSDs) and ergonomic risk practices among medical laboratory professionals in North West Ethiopia. Design: Facility-based cross-sectional study Methods: Cross-sectional study design was employed among medical laboratory professionals (MLPs). The Nordic musculoskeletal questionnaire was adopted and used. In addition to questionnaires about socio-demographic characteristics and ergonomic risk practice, one-to-one interviews, and a direct observational checklist were used. Data was entered into Epi Data 3.1 and then exported and analyzed using SPSS version 25.0. Logistic regression analysis was used to estimate the 95% CI (AOR) at a cut-off value of p <0.05 for statistically significant tests. Results: A total of 238 MLPs participated in the study. The magnitude of WMSDs was 116(48.7%). The most affected body parts were the lower back (20.6%) and wrists (16.4%). The magnitude of WMSDs among government-owned hospitals was the highest (56.4%). 67.6% MLPs never heard about ergonomics. The general mean score of workstations was 2.28. Ergonomic risk practices like repetitive movement and doing of high workload were significantly associated with WMSDs. Conclusion: The current findings revealed a high magnitude of WMSDs that strongly need applying preventive action before body symptoms developed. Improving and renovating workplace design and enhancing awareness of MLPs were the necessary measures to control ergonomic risk factors.