Background Risk factors associated with COVID-19 incidence of death would aid to notify the most favorable management strategies, hang about undecided, Moreover, studies regarding this issue are limited in Ethiopia and no region-wise study is conducted. Hence, the study investigated the COVID-19 incidence of death and its predictors in the Amhara regional state, Ethiopia. Methods A facility-based retrospective survey was conducted at all Amhara regional state COVID-19 treatment centers from 13 March 2020, through 13 January 2022. Epidata version 3.1 and STATA version 14 were used for data entry and analysis, respectively. Linearized survey analysis in a stratified Cox regression model was fitted to identify independent risk factors. P-value with 95% CI for hazard ratio was used for testing the significance at alpha 0.05. Results A total of 28,533 study participants were analyzed in this study. Of these, 2873 (11.2%) died and 25,660 (88.8%) were recovered from COVID-19. The death rate was 11.78 per 1000 person-days of observation with a median survival time of 32 days with IQR [12, 44]. Patients with co-morbidities (AHR = 1.54: 95% CI: 1.51–1.55), patients with age <5-year (AHR = 1.69: 95% CI: 1.78–1.81) and patients with age 60+ years (AHR = 2.91: 95% CI: 1.79–3.99), patients with asymptomatic diseases condition (AHR =1.15: 95% CI: 1.01–1.19), and being male (AHR = 1.22: 95% CI: 1.18–1.27) were independent significant risk factors of death from COVID-19. Conclusion A relatively high incidence of death from COVID-19 was found in this study. Significant risk factors were identified as patients with age <5 years, patients with age 60+ Years, being male, patients having at least one comorbid condition, and patients with asymptomatic disease conditions. These factors should be taken into consideration for a strategy of quarantining and treating COVID-19 patients.