This paper examines the challenges and opportunities in establishing and sustaining north-south research partnerships in Africa through a case study of the UK-Africa Academic Partnership on Chronic Disease. Established in 2006 with seed funding from the British Academy, the partnership aimed to bring together multidisciplinary chronic disease researchers based in the UK and Africa to collaborate on research, inform policymaking, train and support postgraduates and create a platform for research dissemination. We review the partnership’s achievements and challenges, applying established criteria for developing successful partnerships. During the funded period we achieved major success in creating a platform for research dissemination through international meetings and publications. Other goals, such as engaging in collaborative research and training postgraduates, were not as successfully realised. Enabling factors included trust and respect between core working group members, a shared commitment to achieving partnership goals, and the collective ability to develop creative strategies to overcome funding challenges. Barriers included limited funding, administrative support, and framework for monitoring and evaluating some goals. Chronic disease research partnerships in low-income regions operate within health research, practice, funding and policy environments that prioritise infectious diseases and other pressing public health and developmental challenges. Their long-term sustainability will therefore depend on integrated funding systems that provide a crucial capacity building bridge. Beyond the specific challenges of chronic disease research, we identify social capital, measurable goals, administrative support, creativity and innovation and funding as five key ingredients that are essential for sustaining research partnerships.