Abstract Background A growing body of research highlights the pervasive harms of adverse childhood experiences (ACEs) on health throughout the life-course. However, findings from prior reviews and recent longitudinal studies investigating the association between types of ACEs and persistent pain have yielded inconsistent findings in the strength and direction of associations. The purpose of this review is to appraise and summarize evidence on the relationship between ACEs and persistent pain and disability outcomes in adulthood. The specific aims are (1) to determine whether there is a relationship between exposure to ACE and persistent pain and disability in adults and (2) to determine whether unique and cumulative ACEs exposures (number and type) increase the risk of developing persistent pain and disability in adulthood. Method A systematic review and meta-analysis of observational studies will be conducted. Our eligibility criteria are defined following a PECOS approach: population, adults with persistent (≥ 3 months) musculoskeletal and somatoform painful disorders exposed to single or cumulative direct ACEs alone (i.e., physical, sexual, emotional abuse or neglect) or in combination to indirect types of ACE (e.g., parental death, exposure to domestic violence) in the first 18 years of life; comparators, unexposed individuals; outcomes, measurements for persistent pain (≥ 3 months) and disability using discrete and/or continuous measures; and settings, general population, primary care. A comprehensive search of MEDLINE (Ovid) and nine other pertinent databases was conducted from inception to 29 August 2019 using a combination of key words and MeSh terms (the search will be updated prior to conducting the analyses). Pairs of reviewers will independently screen records and full text articles, and a third reviewer will be consulted in cases of disagreement. Data will be extracted using Endnote and Covidence and a meta-analysis will be conducted using Review Manager (RevMan) Version 5.3. The Scottish Intercollegiate Guidelines Network (SIGN) and the Joanna Briggs Institute (JBI) checklists will be used to assess the quality of the included studies. If heterogeneity is high, the findings will be presented in narrative form. Discussion The present review will help consolidate knowledge on persistent pain and disability by evaluating whether frequency and type of adverse childhood experiences produces the most harm. Findings may help inform practitioners and policy-makers who endeavor to prevent and/or mitigate the consequences of ACEs and promote healthy development and well-being of children, youth, and families. Systematic review registration PROSPERO CRD42020150230