Ensuring safe and quality care for patients in hospitals is an important part of a nurse manager's role. Continuous quality improvement has been identified as one approach that leads to the delivery of quality care services to patients and is widely used by nurse managers to improve patient care. Nurse managers’ experiences in initiating continuous quality improvement activities in resource-poor healthcare settings remain largely unknown. Research evidence is highly demanded in these settings to address disease burden and evidence-based practice. This interpretive qualitative study was conducted to gain an understanding of nurse managers’ Continuous Quality Improvement experiences in rural hospitals in Uganda. Nurse managers in rural healthcare settings used their role to prioritize quality improvement activities, monitor the Continuous Quality Improvement process, and utilize in-service education to support continuous quality improvement. The nurse managers in our sample encountered a number of barriers during the implementation of Continuous Quality Improvement, including: limited patient participation, lack of materials, and limited human resources. Efforts to address the challenges faced through good governance and leadership development require more attention.