Sexual harassment is a prevalent yet understudied challenge adolescents face in high school. Because sexual harassment is associated with negative well-being indicators like depression, substance use, and suicidality, school stakeholders must understand its potential consequences for student well-being, and how school climate might impact prevention efforts. The present study investigated whether school climate measures of disciplinary structure, student support, and engagement moderate the relationship between sexual harassment and student well-being. A statewide survey of 85,750 students (grades 9–12) in 322 high schools reported how many times in the past school year they had experienced sexual harassment. Participants also reported school climate perceptions and measures of well-being, including indicators of depression symptoms, substance use, and suicide attempts. Findings indicated that positive perceptions of school climate moderated the relations between sexual harassment experiences and student well-being. The findings from this study will provide valuable information for school stakeholders as they seek to mitigate the impact of sexual harassment in schools.