The joint effect of diabetes mellitus and hypertension on COVID-19 has rarely been evaluated but had potential as a major risk factor. This study aims to investigate the joint effect between diabetes mellitus and hypertension on in-hospital mortality among COVID-19 patients in Yogyakarta stratified by age groups and other comorbidities status. Methods: This cohort retrospective study collected data from two major hospitals in the Sleman district and a total of 2779 hospitalized COVID-19 patients were included in this study. The study outcome was COVID-19 in-hospital mortality (deceased or discharged alive) and the main risk factors were diabetes mellitus (DM) and hypertension (HT). The multiple logistic regression model was utilized to estimate adjusted odds ratio (AOR) and calculate the joint effect. Results: COVID-19 patients who have both DM and hypertension were three times (AOR: 3.21; 95% CI: 2.45–4.19) more likely to have in-hospital mortality than those without both comorbidities. The highest risk of in-hospital mortality was found in COVID-19 patients without other comorbidities (other than DM and HT) and younger age (age 0–40 years), with AOR equal to 22.40 (95% CI: 6.61–75.99). Conclusion: This study identified a joint effect between diabetes mellitus and hypertension which increases the risk of in-hospital mortality among COVID-19 patients. Targeted public health, clinical, and health education intervention should be carried out on individuals with diabetes mellitus and/or hypertension.