The United States has a higher rate of teen pregnancy than any other developed country with 30% of American girls becoming pregnant before the age of 20. Laws regarding the inclusion and content of sexuality education vary across the country, which are associated with differences in pregnancy and sexually transmitted infection (STI) rates between states. This systematic review aims to determine whether comprehensive sexuality education (CSE) is more effective than abstinence-only or no sexuality education at reducing teenage pregnancy. Secondary objectives include analyzing the effect of CSE on STI incidence, sexual activity, safe-sex behaviors, and social discomfort. We searched multiple databases for studies published from 1990 to 2021. Twenty-nine studies met our inclusion criteria. Seven included pregnancy as an outcome, with three fitting our meta-analysis criteria. There was a decrease in pregnancy rates for participants in the CSE intervention compared to the control (n = 3, risk ratio = 0.89, 95%CI 0.79-1.00, I[superscript 2] = 0%). We found that CSE is likely to reduce pregnancy rates; however, there was limited data available on this outcome. CSE increased safe-sex behaviors but did not have a notable impact on sexual activity or STIs. This review can serve as evidence for the implementation of CSE in the US.