Abstract Background The morbidity and mortality of stroke is disproportionately high in developing countries owing to the poor health care system and poor neurologic interventions. Though a number of studies were conducted to estimate the in-hospital mortality rate of stroke in Ethiopia, the lack of a nationwide study that determines the overall magnitude of risk factors and in-hospital mortality rate of stroke is an important research gap. Meta-analysis is key to improve the accuracy of estimates through the use of more data sets. Thus, this study was aimed to determine the overall magnitude of risk factors and in-hospital mortality rate of stroke in Ethiopia. Methods This study was conducted following the PRISMA checklist. We searched from Google Scholar, PubMed, Science Direct, Web of Science, CINAHL, and Cochrane Library databases for studies. Each of the original studies was assessed using a tool for the risk of bias adapted for cross-sectional studies. Data were pooled and a random effect meta-analysis model was fitted to provide the overall magnitude of risk factors and in-hospital mortality rate of stroke. Also, the subgroup analyses were performed to examine how the in-hospital mortality rate varies across different groups of studies. Results In this study, the overall magnitude of hypertension, diabetes mellitus, and atrial fibrillation among stroke patients were 47% (95%CI: 40–54), 8% (95CI%:6–12), and 10% (95%CI: 5–19), respectively. The overall in-hospital mortality of stroke in Ethiopia was 18% (95%:14–22). The highest magnitude of in-hospital mortality of stroke was observed in SNNPR and the lowest was noted in Tigray region. In addition, the magnitude of the in-hospital mortality rate of stroke was 15.1% (95%CI: 11.3–19.4), and 19.6%(95%CI: 14.1–25.7), among studies published before and after 2016, respectively. Conclusions Our pooled result showed that nearly one-fifth of stroke patients have died during hospitalization. The most common risk factor of stroke among the included studies was hypertension followed by atrial fibrillation and diabetes mellitus. There is a need for a better understanding of the factors associated with high blood pressure, especially in countries with a high risk of stroke.