Youths have experienced disruptions to school and home life since the COVID-19 pandemic began in March 2020. During January-June 2021, CDC conducted the Adolescent Behaviors and Experiences Survey (ABES), an online survey of a probability-based, nationally representative sample of U.S. public- and private-school students in grades 9-12 (N = 7,705). ABES data were used to estimate the prevalence of disruptions and adverse experiences during the pandemic, including parental and personal job loss, homelessness, hunger, emotional or physical abuse by a parent or other adult at home, receipt of telemedicine, and difficulty completing schoolwork. Prevalence estimates are presented for all students and by sex, race and ethnicity, grade, sexual identity, and difficulty completing schoolwork. Since the beginning of the pandemic, more than half of students found it more difficult to complete their schoolwork (66%) and experienced emotional abuse by a parent or other adult in their home (55%). Prevalence of emotional and physical abuse by a parent or other adult in the home was highest among students who identified as gay, lesbian, or bisexual (74% emotional abuse and 20% physical abuse) and those who identified as other or questioning (76% and 13%) compared with students who identified as heterosexual (50% and 10%). Overall, students experienced insecurity via parental job loss (29%), personal job loss (22%), and hunger (24%). Disparities by sex and by race and ethnicity also were noted. Understanding health disparities and student disruptions and adverse experiences as interconnected problems can inform school and community initiatives that promote adolescent health and well-being. With community support to provide coordinated, cross-sector programming, schools can facilitate linkages to services that help students address the adverse experiences that they faced during the ongoing COVID-19 pandemic. Public health and health care professionals, communities, schools, families, and adolescents can use these findings to better understand how students' lives have been affected during the pandemic and what challenges need to be addressed to promote adolescent health and well-being during and after the pandemic.