The rapid spread of COVID-19 have overwhelmed health systems, especially in the care of chronic disease such as tuberculosis and diabetes. The objective of the study was to analyze the magnitude and relevance of tuberculosis-diabetes and diabetes-COVID-19 comorbidities in spatial risk areas and their factors associated with unfavorable outcomes in the Brazilian population between 2020 and 2022. An ecological study was carried out in Brazilian municipalities. The population was composed by cases of tuberculosis-diabetes and diabetes-COVID-19 comorbidities, registered in the Influenza Epidemiological Surveillance Information System (SIVEP-GRIPE) and in DATASUS from 2020 to 2022. The Scan Statistics technique was used to identify spatial risk clusters. Binary logistic regression was then employed to understand the relationship between outcomes and comorbidities, considering clinical and sociodemographic variables. A total of 24,750 cases of tuberculosis-diabetes comorbidity were identified, which consisted of an incidence of 3.2 cases per 100,000 inhabitants. Risk clusters were identified in the Central-West and North regions. 303,210 cases of diabetes- COVID-19 comorbidity were identified, resulting in an incidence of 0.4 cases per 100,000 inhabitants. São Paulo-SP, Rio de Janeiro-RJ and Belo Horizonte-MG were the municipalities with the highest spatial risk of illness. The analysis of the spatial risk areas revealed distinct patterns in the geographic distribution of comorbidities. Based on the findings, it is concluded that comorbidities between tuberculosis and diabetes, as well as between COVID-19 and diabetes, represent significant challenges for public health in Brazil, deserving attention from health authorities and the scientific community.