Colorectal cancer (CRC) is the leading cause of death due to cancer worldwide. In Brazil, it is the second most frequent cancer in men and women, with a mortality reaching 9.4% of those diagnosed. The aim of this study was to analyze the spatial heterogeneity of CRC deaths among municipalities in south Brazil, from 2015 to 2019, in different age groups (50–59 years, 60–69 years, 70–79 years, and 80 years old or more) and identify the associated variables. Global Spatial Autocorrelation (Moran’s I) and Local Spatial Autocorrelation (LISA) analyses were used to evaluate the spatial correlation between municipalities and CRC mortality. Ordinary Least Squares (OLS) and Geographically Weighted Regression (GWR) were applied to evaluate global and local correlations between CRC deaths, sociodemographic, and coverage of health care services. For all age groups, our results found areas with high CRC rates surrounded by areas with similarly high rates mainly in the Rio Grande do Sul state. Even as factors associated with CRC mortality varied according to age group, our results suggested that improved access to specialized health centers, the presence of family health strategy teams, and higher rates of colonoscopies are protective factors against colorectal cancer mortality in southern Brazil.