Background: In recent years, a focus has been placed on the increasing rates of suicide in preteens. This is a specific concern for vulnerable sub-populations of preteens, particularly those who experience health disparities or may be underrepresented in suicide research. Little is known about the epidemiology of suicide in preteens, limiting our ability to inform targeted prevention strategies. Methods: This study investigates trends in suicide rates among U.S. preteens aged 8-12 years using national mortality data from the Web-based Injury Statistics Query and Reporting System (WISQARS) between 2001-2020. The number of suicide deaths per year were extracted overall and by sex, race, ethnicity, suicide method, area of residence, and region. Crude rates per 1 million persons were calculated using WISQARS population estimates. Trends in suicide rates were assessed overall, and negative binomial regression models estimated incidence rate ratios to compare period trends. Results: A total of 1930 U.S. youth aged 8-12 years died by suicide from 2001-2020 [573 females (29.7%); 1357 males (70.3%)]. Following a downward trend until 2008, suicide rates significantly increased 10.2% annually from 2009-2020 corresponding to a significant increase in the overall suicide rate between 2001-2008 and 2009-2020. Analyses revealed significant increases among all subgroups, with the greatest increase in females (IRR=3.14; 95% CI=2.53-3.90), American Indian/Alaska Native (AI/AN), Asian/Pacific Islander (A/PI) youth (IRR=3.14; 95% CI=2.53-3.90), and those who died by firearm (IRR=2.29; 95% CI=1.83-2.87). Discussion: Results showing a disproportionate increase in female suicide rates relative to males expands upon existing evidence depicting a narrowing of the historically large gap in youth suicide rates between sexes. Findings further highlight the need to better understand suicide risk among racial and ethnic subgroups, including multiracial individuals who comprise the fastest-growing racial group in the U.S. The current study provides a foundation for future research to explore unique factors associated with preteen suicide. Findings also support the need for culturally informed and developmentally appropriate prevention efforts that emphasize more robust risk screening and lethal means restriction.