Early-onset colorectal cancer incidence rates are rising faster in White individuals than Black individuals. However, prior National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) racial stratification analyses used smaller SEER 13 databases, combined patients under age 50 years, did not stratify by sex, and did not focus on adenocarcinoma histologic subtypes (screening target). To perform a race- and sex-stratified adenocarcinoma incidence rate analysis in individuals aged 40 to 49 years using larger SEER 18 databases with expanded race data to better understand the colorectal cancer burden in those at or approaching screening age. This cross-sectional study used 2000 to 2017 SEER 18 annual age-adjusted colorectal cancer incidence rates stratified by anatomic subsite (colon or rectum), adenocarcinoma histology, race (non-Hispanic Black or non-Hispanic White), and sex for individuals aged 40 to 49 years, and yearly annual percent change (APC) incidence rates were calculated. Annual rate ratios (ARRs) between subgroups were determined. Statistical analysis was performed from January to March 2021. Early-onset colorectal cancer incidence rates, APCs, and ARRs. In this study, a total of 46 728 colorectal cancer cases were identified in 45 429 patients aged 40 to 49 years from 2000 to 2017. Among the 45 429 patients included in this study, 6480 (14.2%) were Black and 27 426 (60.4%) were White; the mean (SD) age was 45.5 (2.8) years. Among White individuals aged 40 to 49 years, colorectal adenocarcinoma incidence rates increased from 19.6 per 100 000 person-years in 2000 to 25.2 per 100 000 person-years in 2017 (APC, 1.6; 95% CI, 1.3 to 1.9). Among Black individuals aged 40 to 49 years, colorectal adenocarcinoma incidence rates were not significantly changed (26.4 per 100 000 person-years in 2000 and 25.8 per 100 000 person-years in 2017 [APC, -0.03; 95% CI, -0.5 to 0.5]). There were no significant differences in ARRs of absolute colorectal incidence rates between White and Black individuals from 2014 to 2017. Rectal-only absolute adenocarcinoma incidence rates in Black and White individuals remained similar from 2000 to 2008 but significantly diverged in 2009. As of 2017, rectal absolute incidence rates were 39% higher among White individuals than among Black individuals with increasing APC (APC, 2.2; 95% CI, 1.6 to 2.8) whereas rectal adenocarcinoma incidence rates among Black individuals were decreasing, although the APC was not statistically significant (APC, -1.4; 95% CI, -2.6 to 0.1). Absolute colonic adenocarcinoma incidence rates remained higher in Black individuals. The study subgroups with the largest divergence in APCs were rectal adenocarcinoma in White vs Black women (APC of 2.2 [95% CI, 1.6 to 2.8] vs APC of -1.7 [95% CI, -3.6 to 0.3], respectively). This study found that colorectal adenocarcinoma incidence rates in people aged 40 to 49 years were increasing among White individuals but stabilized among Black individuals with absolute incidence rates becoming equivalent. Absolute rectal adenocarcinoma incidence rates were 39% lower in Black individuals with a widening disparity in rectal cancer between White and Black women. Possible contributors include introduction of a screening threshold of age 45 years in Black individuals in 2008. Although the average-risk screening age has now shifted to age 45 years in all racial groups, these data can help motivate real-world implementation of guidelines to maximize screening rates that have historically been suboptimal in younger individuals.