Objective: We systematically reviewed and summarized previous studies that examined facilitators and barriers to implementing interventions to increase CRCS uptake in primary care practice.Methods: We searched PubMed, Medline (EBSCO), and CINAHL databases, from the inception of these databases to April 2020. The search strategy combined a set of terms related to facilitators/barriers, intervention implementation, CRCS, and uptake/participation. A priori set inclusion and exclusion criteria were used during both title/abstract screening and full-text screening phases to identify the eligible studies. Quality of the included studies was appraised using quality assessment tools, and data were extracted using a predetermined data extraction tool. We classified facilitators and barriers according to the Consolidated Framework for Implementation Research domains and constructs and identified the common facilitators and barriers looking at how common they were across studies.Results: A total of 12 studies were included in the review. Engagement of the clinic team, leadership team, and partners, clinics' motivation to improve CRCS rates, use of the EMR system, continuous monitoring and feedback system, and having a supportive environment for implementation were the most commonly reported implementation facilitators. Limited time for the clinic team to devote to a new project, challenges in getting accurate, timely data related to CRCS, limited capacity/support to use the EMR system, and disconnect between clinic team members were the most commonly reported implementation barriers.Conclusions: The synthesized findings improve our understanding of facilitators of and barriers to the implementation of interventions to increase CRCS participation in primary care practice, and inform the customized implementation strategies. Many of the included studies had limited use of rigorous implementation science frameworks to guide their implementation and evaluation, which precludes a comprehensive understanding of the implementation factors specific to CRCS interventions in primary care. Future studies assessing the CRCS intervention implementation factors would benefit from the use of implementation science frameworks.