We aimed to investigate the impact of comorbidity burden on mortality in patients with coronavirus disease (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 these patients with and without adjustment for age and sex were calculated. The predictive value of the original Charlson comorbidity index (CCI) and the age-adjusted CCI (ACCI) for mortality in these patients were investigated using the receiver operating characteristic (ROC) curve analysis. Among 7590 patients, 227 (3.0%) had died. After age and sex adjustment, hypertension, diabetes mellitus, congestive heart failure, dementia, chronic pulmonary disease, liver disease, renal disease, and cancer were significant risk factors for mortality. The ROC curve analysis showed that an ACCI threshold > 3.5 yielded the best cut-off point for predicting mortality (area under the ROC 0.92; 95% confidence interval 0.91–0.94). Our study revealed multiple risk factors for mortality in patients with COVID-19. The high predictive power of the ACCI for mortality in our results can support the importance of old age and comorbidities in the severity of COVID-19.