Background Health measurement guides policies and health care decisions are necessary to describe and attain the quintuple aim of improving patient experience, population health, care team well-being, health care costs, and equity. In the primary care setting, patient-reported outcome measurement allows outcome comparisons within and across settings and helps improve the clinical management of patients. However, these digital patient-reported outcome measures (PROMs) are still not adapted to the clinical context of primary health care, which is an indication of the complexity of integrating these tools in this context. We must then gather evidence of their impact on chronic disease management in primary health care and understand the characteristics of effective implementation. Objective We will conduct a systematic review to identify and assess the impact of electronic PROMs (ePROMs) implementation in primary health care for chronic disease management. Our specific objectives are to (1) determine the impact of ePROMs in primary health care for chronic disease management and (2) compare and contrast characteristics of effective ePROMs’ implementation strategies. Methods We will conduct a systematic review of the literature in accordance with the guidelines of the Cochrane Methods Group and in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for its reporting. A specific search strategy was developed for relevant databases to identify studies. Two reviewers will independently apply the inclusion criteria using full texts and will extract the data. We will use a 2-phase sequential mixed methods synthesis design by conducting a qualitative synthesis first, and use its results to perform a quantitative synthesis. Results This study was initiated in June 2022 by assembling the research team and the knowledge transfer committee. The preliminary search strategy will be developed and completed in September 2022. The main search strategy, data collection, study selection, and application of inclusion criteria were completed between October and December 2022. Conclusions Results from this review will help support implementation efforts to accelerate innovations and digital adoption for primary health care and will be relevant for improving clinical management of chronic diseases and health care services and policies. Trial Registration PROSPERO International Prospective Register of Systematic Reviews CRD42022333513; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=333513 International Registered Report Identifier (IRRID) DERR1-10.2196/48155