Background: Limited research exists on the process of applying knowledge translation (KT) methodology to a rural-based population health intervention. Methods: This study reports on the implementation and translational stages of a previously described Co-creating KT (Co-KT) framework in the rural town of Port Lincoln, South Australia (population: 14,000). The Co-KT framework involves five steps: (i) collecting local data; (ii) building stakeholder relationships; (iii) designing an evidence-based intervention incorporating local knowledge; (iv) implementation and evaluation of the intervention; and (v) translating the research into policy and practice. Barriers and enablers to the overall Co-KT implementation process were identified. Our intervention focused on musculoskeletal (MSK) conditions. Results: Although the Co-KT framework was valuable in engaging with the community, translating the final intervention into daily clinical practice was prevented by a lack of an accessible policy or financial framework to anchor the appropriate intervention, a lack of continued engagement with stakeholders, access problems to general practitioners (GPs) and Allied Health Professionals; and the paucity of referrals from GPs to Allied Health Professionals. Consequently, while many aspects of the intervention were successful, including the improvement of both function and pain in study participants, the full implementation of the Co-KT framework was not possible. Discussion: This study implemented and evaluated a Co-KT framework for a population with MSK conditions, linking locally generated health care system knowledge with academic input. Further policy, health system changes, and on-the-ground support are needed to overcome the identified implementation challenges in order to create sustainable and effective system change.