The COVID-19 pandemic has impacted health systems worldwide. Studies to date have largely focused on the health care system with less attention to the impact on public health systems and practice. Objective: To describe the early impacts of COVID-19 on public health systems and practice in 3 Ugandan districts from the perspective of public health system leaders and synthesize lessons learned. Design: A qualitative study using semi structured virtual interviews with public health leaders between October 2020 and April 2021. The World Health Organizations essential public health operations framework guided data collection and analysis. Setting: This study involved the Ugandan government. These districts were chosen for their large populations, relatively high COVID-19 burden, and variation in public health systems. Participants: Public health leaders from Kampala (n = 21), Wakiso (n = 18), and Mubende (n = 19) in organizations with a primary mandate of stewardship and/or administration of essential public health operations (total n = 58). Results: We found that the COVID-19 pandemic led to intensified collaboration in public health systems and a change in workforce capacity to respond to the pandemic. This came with opportunities but also challenges of burnout and disruption of non-COVID-19 services. Information systems and digital technologies were increasingly used and there was greater proximity between public health leaders and other health system leaders. A renewed recognition for public health work was also highlighted. Conclusions: The COVID-19 pandemic impacted several aspects of public health systems in the provinces studied. Our findings can help public health leaders and policy makers identify areas for further investment (eg, intersectoral collaboration, information systems) and develop plans to address challenges (eg, disrupted services, workforce burnout) that have surfaced.