Primary care offers a familiar and accessible clinical venue for patients with obesity to receive evidence-based lifestyle interventions for weight management. However, there are numerous barriers to the implementation of such programs in primary care, and previous primary care weight loss interventions demonstrate modest and temporary effects. Weight loss treatment delivered within primary care by peer coaches may offer a viable and effective alternative. The purpose of this trial is to test the effects of weight loss treatment that includes ongoing support from a peer coach (i.e., trained, salaried community health workers) as compared to self-directed treatment. Peer coach treatment will be delivered over 18 months and includes a combination of in-person, group-based office visits and individual telephone contacts. This weight loss trial will include 375 adults with obesity (BMI = 30–50 kg/m2) randomized from 10 primary care practices. The primary outcome will be changes in body weight at month 18. Secondary outcomes will include key patient-centered outcomes, including quality-of-life, physical and social functioning, mood, and treatment satisfaction. The cost-effectiveness of the peer coach intervention will also be evaluated. If this novel intervention is effective, it could offer a practical and sustainable approach for the delivery of weight loss treatment in primary care that has the potential to improve clinical outcomes for patients, increase treatment options for primary care providers, and reduce obesity-related healthcare utilization and costs.