The COVID-19 pandemic, caused by SARS-CoV-2, led to 622,119,701 reported cases and 6,546,118 deaths. Most studies on COVID-19 patients in hospitals are from high-income countries, lacking data for developing countries such as Ethiopia.This study assesses clinical features, demographics, and risk factors for in-hospital mortality in Hawassa, Ethiopia. The research cohort comprises 804 cases exhibiting clinical diagnoses and/or radiological findings and indicative of symptoms consistent with COVID-19 at Hawassa University Comprehensive Specialized Hospital from September 24, 2020, to November 26, 2021. In-hospital mortality rate was predicted using Cox regression. The median age was 45 years, with males making up 64.1% of the population. 173 (21.5%) fatalities occurred, with 125 (72.3%) among males. Male patients had higher mortality rates than females. Severe and critical cases were 24% and 21%. 49.1% had at least one comorbidity, with 12.6% having multiple. Common comorbidities were diabetes (15.9%) and hypertension (15.2%). The Cox regression in Ethiopian COVID-19 patients found that factors like gender, advanced age group, disease severity, symptoms upon admission, shortness of breath, sore throat, body weakness, hypertension, diabetes, multiple comorbidities, and prior health facility visits increased the risk of COVID-19 death, similar to high-income nations. However, in Ethiopia, COVID-19 patients were young and economically active. Patients with at least one symptom had reduced death risk. As a conclusion, COVID-19 in Ethiopia mainly affected the younger demographic, particularly economically active individuals. Early detection can reduce the risk of mortality. Prompt medical attention is essential, especially for individuals with comorbidities. Further research needed on diabetes and hypertension management to reduce mortality risk. Risk factors identified at admission play a crucial role in guiding clinical decisions for intensive monitoring and treatment. Broader risk indicators help prioritize patients for allocation of hospital resources, especially in regions with limited medical facilities. Government’s focus on timely testing and strict adherence to regulations crucial for reducing economic impact.