We aimed to investigate the impact of comorbidity burden on mortality in patients with COVID-19. We analyzed the COVID-19 data from the nationwide health insurance claims of South Korea. Data on demographic characteristics, comorbidities, and mortality records of patients with COVID-19 were extracted from the database. The odds ratios of mortality according to comorbidities in patients with COVID-19 with and without adjustment for age TRANS and sex were calculated. The predictive value of the original Charlson comorbidity index (CCI) and the age TRANS-adjusted CCI (ACCI) for mortality in patients with COVID-19 were investigated using the receiver operating characteristic (ROC) curve analysis. Among 7,590 patients with COVID-19, 227 (3.0%) had died. After age TRANS and sex adjustment, hypertension MESHD hypertension HP, diabetes mellitus MESHD diabetes mellitus HP, congestive heart failure HP heart failure MESHD, dementia MESHD dementia HP, chronic pulmonary disease, liver MESHD, renal, and cancer were significant risk factors for mortality. The ROC curve analysis showed that ACCI threshold ≥4 yielded the best cut-off point for predicting mortality (area under the ROC 0.92; 95% CI, 0.91–0.94). Our study revealed multiple risk factors that were associated with mortality in patients with COVID-19. The high predictive power of the ACCI for mortality in our results could support the importance of old age TRANS and comorbidities in the severity of COVID-19.