Anterior cruciate ligament (ACL) injuries account for a large percentage of knee injuries, disproportionately affecting female athletes. To help health professionals stay current, we performed an umbrella review to evaluate the effectiveness of ACL injury prevention programs in reducing non-contact ACL injury rates, determine the effective components within interventions, and provide clinical recommendations. Twelve databases (Medline, Embase, Cochrane Database of Systematic Reviews, SPORTDiscus, Cumulative Index to Nursing and Allied Health Literature, PEDro, Web of Science, Epistemonikos, TRIP, BC Guidelines and Protocols, CPG Infobase, ProQuest Dissertations and Theses Global) were searched in May 2021 to identify relevant systematic reviews and meta-analyses. Four databases were searched again in September 2021 to identify recent primary literature. Non-contact ACL injury data were extracted to calculate incidence rate ratios (IRRs) and these were combined using an inverse variance random-effects model. A qualitative assessment of included reviews was performed. The methodological quality of the studies was assessed using a Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) or Cochrane Risk-of-Bias Tool for Randomized Trials (RoB 2). Sixteen reviews and two primary studies met the inclusion criteria. Across 11 primary studies, prevention programs were effective in reducing non-contact ACL injuries by 64% (IRR = 0.36 (95% CI: 0.18–0.70)). A multi-faceted exercise program, beginning in the pre-season and containing at least three exercise types, may be beneficial in reducing ACL injury risk.