Objective: To analyze the time series of colorectal cancer (CRC) mortality, according to sex and age group, in Mato Grosso, Brazil, from 2000 to 2019. Methods: Ecological time series study, with standardized mortality rates from CRC (C18 to C21) among residents of Mato Grosso. Information on deaths was provided by the Mato Grosso State Health Department, comprising the Mortality Information System and demographic information obtained from the Brazilian Institute of Geography and Statistics. The joinpoint regression analysis was used in the analysis of temporal trend. Results: A total of 2,406 deaths from CRC were identified in Mato Grosso between 2000 and 2019. The highest rates were found among the age group from 60 to 79 years. There was an increasing trend in mortality rates among men due to CRC for almost all age groups, with the exception of those aged 40 to 49 years and 80 years and older. For women, there was a significant increase in the age groups from 50 to 59 years and 80 years and older. Conclusion: The results showed an increase in mortality rates from CRC in the state of Mato Grosso, from 2000 to 2019, in certain age groups for both sexes, but especially for men. Knowledge about the evolution of mortality can provide data on the epidemiological situation of cancer at the local level and, thus, contribute to the development of actions to control and prevent this disease.