Adverse childhood experiences (ACEs) have been associated with causes of early death, addiction, mental illness, and poor health. However, studies investigating underlying mechanisms often rely on cross-sectional data or inappropriate study designs. To prevent the negative sequelae associated with ACEs, it is imperative to understand the mechanisms underlying the prospective relationship. The aim of this present review was to provide a synthesis and critical evaluation of the literature regarding the mechanisms underlying this relationship. A search in SCOPUS, MedLine via Ovid, PsycINFO via Ovid, and Web of Science was performed. Studies that utilised a prospective design assessing ACEs in childhood or adolescence, outcomes in adulthood, and analysed either a mediating or moderating relationship were included, unless the study relied on informant report or official records to assess childhood maltreatment types of ACEs. Twenty-two studies examining a longitudinal mediation or moderation were included in a systematic review. A review of the studies found links to psychopathology, delinquent and problem behaviours, poor physical health, and poor socioeconomic outcomes. A clear image of underlying mechanisms is not forthcoming due to (a) poor study design in relation to assessing longitudinal mechanisms, and (b) heterogeneity in the adversities, mechanisms, and outcomes assessed. Based on the review, several gaps and limitations are highlighted and discussed.