Background: Prenatal alcohol exposure can result in a wide range of adverse health outcomes, including in some cases fetal alcohol spectrum disorder (FASD), a lifelong neurodevelopmental disorder. Thus, there is pressing need for effective interventions to prevent alcohol-exposed pregnancies (AEPs). Methods: A systematic review was undertaken to provide an up-to-date analysis of the current prevention literature. PubMed, Embase, CINAHL, and PsycINFO were searched for relevant English-language articles published from 1970 onward. Studies were eligible for the current systematic review if the interventions included pregnant and postpartum women and/or their support networks to prevent AEPs and FASD. Outcomes of interest included alcohol consumption, knowledge, contraceptive use, neonatal outcomes, family well-being or functioning, economics, and healthcare utilization outcomes. Results: Thirty-four peer-reviewed studies met the inclusion criteria. Fifteen studies employed brief intervention (BI) methods, 6 used long-term/intensive strategies, and 5 were educational interventions. A further 3 studies assessed counseling approaches, 2 evaluated multicomponent interventions, and 3 assessed nutritional supplementation interventions. Conclusions: The current review identified variable results from available interventions to prevent alcohol use among pregnant and postpartum women. Preliminary evidence demonstrated that BIs may be effective among subgroups of pregnant women with higher initial alcohol consumption, those with partner involvement, and those who used alcohol and other substances concurrently. Some preliminary evidence relating to long-term interventions with pregnant women with polysubstance use emerged, specifically case management that not only focused on reduction in substance use, but also on addressing the complex interplay between health and social well-being of families. Overall, additional research is required to improve the effectiveness of preventative approaches during pregnancy and the postpartum period.