Background: Colorectal cancer (CRC) represents a growing public health challenge globally, with considerable heterogeneity in incidence and mortality across middle-income countries. Demographic transitions, lifestyle-related risk factors, and unequal access to early detection and treatment shape the CRC burden.

Objectives: To compare incidence (2000–2020) and mortality (2000–2023) trends between early-onset (<50 years) and late-onset (≥50 years) CRC in Brazil and to evaluate age, period, and birth cohort effects on CRC incidence and mortality.

Methods: We conducted a population-based ecological study using data from Brazilian population-based cancer registries, the Mortality Information System of the Ministry of Health, and national census and intercensal population estimates. Analyses were stratified by sex (male and female), geographic region (North, Northeast, Midwest, Southeast, and South), and age group. Age-standardized incidence rates (ASIRs) and mortality rates (ASMRs) were calculated using the direct method and Segi’s world standard population. Temporal trends were assessed using Joinpoint regression to estimate annual percent change and average annual percent change (AAPC). Age–period–cohort (APC) analyses were performed using Poisson regression models to separate age, calendar period, and birth cohort effects, expressed as relative risks (RRs) relative to the 2000–2004 reference period and the 1955 birth cohort.

Results: Between 2000 and 2020, 127,813 new CRC cases were diagnosed in Brazil among individuals aged ≥25 years, and 344,250 CRC deaths were recorded between 2000 and 2023. The overall ASIR was 39.0 per 100,000 among males and 32.5 per 100,000 among females. Among early-onset CRC, females exhibited slightly higher ASIRs than males in most regions, except in the South. In contrast, late-onset CRC incidence was consistently higher among males across all regions and nationwide. CRC incidence increased significantly in Brazil for both sexes (males: AAPC 0.91%; females: AAPC 0.73%). Early-onset CRC incidence increased in the North, Northeast, and Southeast regions for both males and females, whereas late-onset incidence remained stable in the South and Southeast. ASMR increased significantly across all regions, sexes, and age groups, with marked increases observed in the North and Northeast for both early- and late-onset CRC among males and females. APC analyses showed a strong age effect, with ASIRs and ASMRs increasing progressively from ages 25–29 to ≥80 years and accelerating after age 50. Period effects for incidence in Brazil showed modest increases during intermediate periods (approximately 7–12%), followed by stabilization in the most recent period, whereas mortality period effects increased steadily over time. Cohort analyses revealed clear generational gradients: compared with the 1955 birth cohort, individuals born after the mid-1960s experienced progressively higher CRC incidence and mortality risks, particularly for early-onset CRC. These cohort effects were more pronounced in the North and Northeast regions.
 
Conclusions: The incidence and mortality of CRC in Brazil have increased over time, with marked differences between regions. Early-onset CRC shows stronger cohort-driven increases in risk, particularly among females from Northeast, whereas late-onset CRC remains largely driven by age. These findings underscore the importance of region-specific prevention strategies and support consideration of earlier, risk-adapted CRC screening approaches in Brazil.