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The literature remains scarce regarding the varying point estimates of risk factors for COVID-19 associated mortality and hospitalization. This meta-analysis investigates risk factors for mortality and hospitalization, estimates individual risk factor contribution, and determines drivers of published estimate variances. We conducted a systematic review and meta-analysis of COVID-19 related mortality and hospitalization risk factors using PRISMA guidelines. Random effects models estimated pooled risks and meta-regression analyses estimated the impact of geographic region and study type. Studies conducted in North America and Europe were more likely to have lower effect sizes of mortality attributed to chronic kidney disease (OR: 0.21, 95% CI: 0.09–0.52 and OR: 0.25, 95% CI: 0.10–0.63, respectively). Retrospective studies were more likely to have decreased effect sizes of mortality attributed to chronic heart failure compared to prospective studies (OR: 0.65, 95% CI: 0.44–0.95). Studies from Europe and Asia (OR: 0.42, 95% CI: 0.30–0.57 and OR: 0.49, 95% CI: 0.28–0.84, respectively) and retrospective studies (OR: 0.58, 95% CI: 0.47–0.73) reported lower hospitalization risk attributed to male sex. Significant geographic population-based variation was observed in published comorbidity related mortality risks while male sex had less of an impact on hospitalization among European and Asian populations or in retrospective studies.