Suicide is the third leading cause of death among high school-aged youths aged 14–18 years. The 2021 suicide rate for this age group was 9.0 per 100,000 population. Updating a previous analysis of the Youth Risk Behavior Survey during 2009–2019, this report uses 2019 and 2021 data to examine high school students’ reports of suicidal thoughts and behaviors. Prevalence estimates are reported by grade, race and ethnicity, sexual identity, and sex of sexual contacts. Unadjusted logistic regression models were used to calculate prevalence differences comparing 2019 to 2021 and prevalence ratios comparing suicidal behavior between subgroups across demographic characteristics to a referent group. From 2019 to 2021, female students had an increased prevalence of seriously considered attempting suicide (from 24.1% to 30%), an increase in making a suicide plan (from 19.9% to 23.6%), and an increase in suicide attempts (from 11.0% to 13.3%). In addition, from 2019 to 2021, Black or African American (Black), Hispanic or Latino (Hispanic), and White female students had an increased prevalence of seriously considered attempting suicide. In 2021, Black female students had an increased prevalence of suicide attempts and Hispanic female students had an increased prevalence of suicide attempts that required medical treatment compared with White female students. Prevalence of suicidal thoughts and behaviors remained stable overall for male students from 2019 to 2021. A comprehensive approach to suicide prevention with a focus on health equity is needed to address these disparities and reduce prevalence of suicidal thoughts and behaviors for all youths. School and community-based strategies include creating safe and supportive environments, promoting connectedness, teaching coping and problem solving, and gatekeeper training.