The capacity to engage in research, evaluation and evidence-informed decision-making supports effective public health policy and practice. Little is known about partnership-based approaches that aim to build capacity across a system or how to evaluate them. This study examines the impacts of a research and evaluation capacity building partnership called the Western Australian Sexual Health and Blood-borne Virus Applied Research and Evaluation Network (hereafter, SiREN). SiREN aims to strengthen capacity across a system of clinical and medical services and government and non-government organizations. These organizations are connected through their shared aim of preventing and managing sexually transmissible infections and blood-borne viruses. To examine SiREN, systems concepts and methods were used. Data were collected from SiREN organizational documents (n = 42), a survey tool (n = 104), in-depth interviews (n = 17), a workshop and three meetings with SiREN stakeholders and used to develop two causal loop diagrams. Findings show engagement with SiREN was influenced by a complex interplay of contextual (e.g., organizational capacity) and process (e.g., presence of trusting relationships) factors. SiREN contributed to system level changes, including increased resources for research and evaluation, the development of networks and partnerships that led to more efficient responses to emerging health issues, evidence sharing, and sustainable research and evaluation practice. The use of causal loop diagrams enabled the identification of key leverage points that SiREN can use for continuous improvement or evaluation. The focus on how contextual factors influenced SiREN's ability to create change provides valuable information for researchers, policymakers or practitioners seeking to develop a similar partnership.