Collaboration between clinical and community-based social service organizations is increasingly seen as vital for preventing and managing chronic diseases but has been challenging to establish and sustain. The aim of this study was to identify organizational barriers and facilitators for clinic-community collaboration. We employed multiple methods to study a national sample of nonprofit community-based organizations that each collaborated with local clinical organizations for diabetes prevention in the United States. We used qualitative data collected longitudinally through 65 semistructured interviews from 2016 to 2017 at seven of these organizations and their clinical collaborators to understand their relationships. We employed survey data ( N = 247 with 73% response rate) to measure and explore relationships among qualitatively identified themes and collaboration performance. We documented three levels of organizational challenges to community-clinic collaboration. Interorganizational challenges pertain to facing only weakly aligned interests across organizations. Interpersonal challenges pertain to misperceptions and miscommunications that occur as frontline employees from differing organizations seek to work together. Task-related challenges pertain to the inadequacy of current processes to effectively link services across clinical and community settings. We found that bridging leadership , provisional teamwork, and learning processes helped to overcome these challenges by enabling iterative progress. Follow-up national survey results indicated that these facilitators were significantly associated with collaboration performance. Because community-clinic collaboration presents substantial interorganizational, interpersonal, and task-related challenges, financial incentives alone are likely insufficient for success. Resources that help develop capacity to work across community and clinical settings may be vital and warrant dedicated funding.