Background: Depression is a leading cause of major public health problems globally, and its frequency has been increasing, particularly in low- and middle-income countries. The prevalence of depression in sub-Saharan Africa ranges from 15 to 30%. In Ethiopia, depression is found to be the seventh leading cause of disease burden, yet no study was done in West Shewa, Ethiopia. Therefore, this study aimed to assess the magnitude of depression and associated factors among adult orthopedic outpatients getting treatment at Ambo University Referral Hospital, West Shewa, Oromia, Ethiopia, in 2023. Methods: An institution-based cross-sectional study was conducted among 391 adult orthopedic patients from January 1–30, 2023. A systematic random sampling technique was used to select the study subjects. The data were collected by using a structured questionnaire and checklist through face-to-face interview and chart review techniques. The collected data were entered into Epi-data version 4.6 and then exported to SPSS version 26.0 for statistical analysis. The binary logistic regression model was fitted, and both bi-variable and multi-variable logistic regression analyses were employed. Result: The magnitude of depression was found to be 38.9% (95% CI: 34.5%, 43.9%), being female (AOR=2.41; 95% CI: 1.45–4.00), chewing chat (AOR=2.39; 95% CI: 1.29–4.43), and no disorder on the lower limb (AOR=0.24; 95% CI: 0.07–0.85). had ligament injury (AOR=2.62; 95% CI: 1.23-5.59), had no complication (AOR=0.07; 95% CI: 0.01-0.52), and had amputation (AOR=3.83; 95% CI: 2.09-7.00) were significantly associated with depression. Conclusion and Recommendation: The study found that the prevalence of depression among orthopedic patients was considerable; nearly half of the participants developed depression at Ambo University Referral Hospital, and being female, chewing chat, having no disorder on the lower limb, having a ligament injury, having a complication, and being amputated were significantly associated with depression. Therefore, due attention is needed from concerned bodies in order to tackle this problem.