Background Stroke is one of the leading causes of death and disability in developing countries. The burden of stroke has varied widely in different areas, and there is a paucity of information about stroke in the selected study area. Objectives To assess the burden, risk factors, and outcomes of stroke at Debre Markos Referral Hospital, Northwest Ethiopia Patients and methods A hospital-based retrospective observational study was conducted in the medical ward of Debre Markos Referral Hospital from March 2017 to April 2019. A pretested checklist was used to extract relevant data from the chart of stroke patients. All statistical analyses were performed in the SPSS version 20 software. Results From a total of 2100 admissions in the medical ward, 162 of them were stroke patients, giving the in-hospital magnitude of 7.7%. The in-hospital case fatality rate was 8.6%. Additionally, 27.2% of patients were improved and 39.5% of them were referred. There was a significant association between types of stroke and risk factors such as sex, comorbid hypertension, hyperlipidemia, and atrial fibrillation (P ≤ 0.05). Conclusion The in-hospital period prevalence of stroke was 7.7%. Ischemic stroke was the most common type of stroke. Hypertension and hyperlipidemia were the leading identified risk factors for stroke. The overall in-hospital mortality was lower than previous studies in sub-Saharan African countries. Therefore, effective strategies and guidelines for the prevention and control of stroke and its risk factors are needed.