Local health departments (LHDs) are positioned to act as the community health strategist for their catchment area, which requires cross-sector collaboration. However, little research exists to understand how much and what types of cross-sector collaboration occur and its impact on LHD practice. Data from 490 LHDs who participated in the 2016 National Profile of Local Health Departments survey were analyzed to identify patterns of cross-sector collaboration among LHDs. In the survey, LHDs reported the presence of collaborative activities for each of 22 categories of organizations. Factor analysis was used to identify patterns in the types of organizations with which LHDs collaborate. Then, cluster analysis was conducted to identify patterns in the types of cross-sector collaboration, and cross-sectional analyses examined which LHD characteristics were associated with cluster assignment. LHDs collaborated most with traditional health care–oriented organizations, but less often with organizations focused on upstream determinants of health such as housing. Three distinct clusters represented collaboration patterns in LHDs: coordinators, networkers, and low-collaborators. LHDs who were low-collaborators were more likely to serve smaller populations, be unaccredited, have a smaller workforce, have a White top executive, and have a top executive without a graduate degree. These findings imply that public health practitioners should prioritize building bridges to a variety of organizations and engage in collaboration beyond information sharing. Furthermore, LHDs should prioritize accreditation and workforce development activities for supporting cross-sector collaboration. With these investments, the public health system can better address the social and structural determinants of health and promote health equity.