Predictive tools provide a unique opportunity to explain the observed differences in outcome between patients of the COVID-19 pandemic. The aim of this study was to associate individual demographic and clinical characteristics with disease severity in COVID-19 patients and to highlight the importance of machine learning (ML) in disease prognosis. The study enrolled 344 unvaccinated patients with confirmed SARS-CoV-2 infection. Data collected by integrating questionnaires and medical records were imported into various classification machine learning algorithms, and the algorithm and the hyperparameters with the greatest predictive ability were selected for use in a disease outcome prediction web tool. Of 111 independent features, age, sex, hypertension, obesity, and cancer comorbidity were found to be associated with severe COVID-19. Our prognostic tool can contribute to a successful therapeutic approach via personalized treatment. Although at the present time vaccination is not considered mandatory, this algorithm could encourage vulnerable groups to be vaccinated.