Many high- and middle-income countries (HMICs) are experiencing a burden of comorbidity and chronic diseases. Together with increasing patient expectations, this burden is raising demand for population health–oriented innovation in health care. Using desk review and country case studies, we examine strategies applied in HMICs outside the United States to address these challenges, with a focus on and use of a new framework for analyzing primary care (PC). The article outlines how a population health approach has been supported by focusing assessment on and clustering services around social groups and multimorbidity, with support for community roles. It presents ways in which early first contact and continuity of PC, PC coordination of referral, multidisciplinary team approaches, investment in PC competencies, and specific payment and incentive models have all supported comprehensive approaches. These experiences locate PC as a site of innovation, where information technology and peer-to-peer learning networks support learning from practice.