Background. Exercise and physical activity are a core component of knee osteoarthritis (OA) care, yet access to physical therapists is limited for many people. Telephone service delivery models may increase access. Objective. Determine the effectiveness of incorporating exercise advice and behavior change support by physical therapists into an existing Australian nurse-led musculoskeletal telephone service for adults with knee OA. Design. Randomized controlled trial with nested qualitative studies Setting. Community, Australia-wide Participants. One hundred seventy-five people ≥45 years of age with knee symptoms consistent with a clinical diagnosis of knee OA. Eight musculoskeletal physical therapists will provide exercise advice and support. Intervention. Random allocation to receive existing care or exercise advice in addition to existing care. Existing care is a minimum of one phone call from a nurse for advice on OA self-management. Exercise advice involves 5–10 calls over 6 months from a physical therapist trained in behavior change support to prescribe, monitor, and progress a strengthening exercise program and physical activity plan. Measurements. Outcomes will be measured at baseline and at 6 and 12 months. Primary outcomes are knee pain and physical function. Secondary outcomes include other measures of knee pain, self-efficacy, physical activity and its mediators, kinesiophobia, health service usage, work productivity, participant-perceived change, and satisfaction. Additional measures include adherence, adverse events, therapeutic alliance, satisfaction with telephone-delivered therapy, and expectation of outcome. Semi-structured interviews with participants with knee OA and therapists will be conducted. Limitations. Physical therapists cannot be blinded. Conclusions. This study will determine if incorporating exercise advice and behavior change support by physical therapists into a nurse-led musculoskeletal telephone service improves outcomes for people with knee OA. Findings will inform development and implementation of telerehabilitation services.