Background: The novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in China and later spread rapidly to other parts of the world, including Africa. Africa was projected to be devastated by COVID-19. There is currently limited data regarding regional predictors of mortality among patients with COVID-19. This study aimed to evaluate the independent risk factors associated with mortality among patients with COVID-19 in Africa. Methods: A total of 1028 confirmed cases of COVID-19 from Africa with definite survival outcomes were identified retrospectively from an open-access individual-level worldwide COVID-19 database. The live version of the dataset is available at https://github.com/beoutbreakprepared/nCoV2019. Multivariable logistic regression was conducted to determine the risk factors that independently predict mortality among patients with COVID-19 in Africa. Results: Of the 1028 cases included in study, 432 (42.0%) were females with a median (interquartile range, IQR) age of 50 (24) years. Older age (adjusted odds ratio {aOR} 1.06; [95% confidence intervals {95% CI}, 1.04–1.08]), presence of chronic disease (aOR 9.63; [95% CI, 3.84–24.15]), travel history (aOR 2.44; [95% CI, 1.26–4.72]), as well as locations of Central Africa (aOR 0.14; [95% CI, 0.03–0.72]) and West Africa (aOR 0.12; [95% CI, 0.04–0.32]) were identified as the independent risk factors significantly associated with increased mortality among the patients with COVID-19. Conclusions: The COVID-19 pandemic is evolving gradually in Africa. Among patients with COVID-19 in Africa, older age, presence of chronic disease, travel history, and the locations of Central Africa and West Africa were associated with increased mortality. A regional response should prioritize strategies that will protect these populations. Also, conducting a further in-depth study could provide more insights into additional factors predictive of mortality in COVID-19 patients. © 2020, W. Montague Cobb-NMA Health Institute.