: Prior data showed an increasing incidence of early-onset colorectal cancer (EO-CRC) in the US. However, there are limited comprehensive data on recent EO-CRC incidence and mortality per different age cohorts and tumor characteristics. We aimed to evaluate EO-CRC incidence and mortality in different populations. : Age-adjusted EO-CRC incidence rates were calculated from the USCS database between 2001 and 2021. Age-adjusted EO-CRC mortality rates were calculated from the NCHS database between 2000 and 2022 and the SEER database between 2004 and 2021. The age groups were 20-44 years and 45-54 years. Tumors were categorized by anatomical location (right, transverse, left, and proximal) and stage at diagnosis (early and late). The annual and average annual percentage changes (AAPC) were estimated using joinpoint regression. Age-specific pairwise comparison was conducted. : A total of 474,601 patients were diagnosed with EO-CRC between 2001 and 2021. The EO-CRC incidence increased in patients aged 20-44 years faster than in those aged 45-54 years (AAPC = 1.51 vs. 0.73; AAPC difference = 0.78, = 0.001). This was most notable in proximal colon tumors (AAPC difference = 0.88, < 0.001). While the incidence of early-stage tumors decreased in recent years across all anatomical locations, late-stage tumors increased, mostly in the proximal colon (AAPC = 2.44). A total of 147,026 patients died from EO-CRC between 2000 and 2022. Mortality increased in patients aged 20-44 years faster than in patients aged 45-54 years, who had a stable trend (AAPC difference = 0.85, < 0.001). The increase in mortality was noted in both early- and late-stage tumors. : Our study provides epidemiologic evidence showing an alarming increase in EO-CRC incidence and mortality among patients aged 20-44 years compared to those aged 45-54 years, which is associated with delayed diagnosis, and mostly in proximal colon tumors. Expanding screening efforts to younger populations and addressing healthcare disparities are essential for improving early detection and outcomes for younger patients.