Objective: Although Indigenous women are exposed to high rates of risk factors for perinatal mental health problems, the magnitude of their risk is not known. This lack of data impedes the development of appropriate screening and treatment protocols, as well as the proper allocation of resources for Indigenous women. The objective of this systematic review and meta-analysis was to compare rates of perinatal mental health problems among Indigenous and non-Indigenous women. Methods: We searched Medline, EMBASE, PsycINFO, CINAHL, and Web of Science from their inceptions until February 2019. Studies were included if they assessed mental health in Indigenous women during pregnancy and/or up to 12 months postpartum. Results: Twenty-six articles met study inclusion criteria and 21 were eligible for meta-analysis. Indigenous identity was associated with higher odds of mental health problems (odds ratio [ OR] 1.62; 95% confidence interval [CI], 1.25 to 2.11). Odds were higher still when analyses were restricted to problems of greater severity ( OR 1.95; 95% CI, 1.21 to 3.16) and young Indigenous women ( OR 1.86; 95% CI, 1.51 to 2.28). Conclusion: Indigenous women are at increased risk of mental health problems during the perinatal period, particularly depression, anxiety, and substance misuse. However, resiliency among Indigenous women, cultural teachings, and methodological issues may be affecting estimates. Future research should utilize more representative samples, adapt and validate diagnostic and symptom measures for Indigenous groups, and engage Indigenous actors, leaders, and related allies to help improve the accuracy of estimates, as well as the well-being of Indigenous mothers, their families, and future generations. Trial Registration: PROSPERO-CRD42018108638.