In 1971, Congress passed the National Cancer Act, landmark legislation that reorganized the National Institutes of Health's National Cancer Institute (NCI). The Act included a new focus on cancer control, including the requirement that the NCI award research grants and contracts, in collaboration with other public agencies and private industry, to conduct cancer control activities related to the diagnosis, prevention, and treatment of cancer. The requirement placed the NCI at the nexus of a rapidly changing science and a complex and dynamic healthcare delivery system and involved an evolutionary transformation to advance cancer control and cancer care delivery research along the cancer care continuum. Analysis is based on a qualitative ethnographic approach using historical records, oral histories, and targeted interviews. The multimethod approach provided the opportunity to describe the vision, leadership, and struggle to build an infrastructure, expand expertise, and forge collaboration with the NCI and a complex and changing healthcare system. As the 50th anniversary of the National Cancer Act approaches in 2021, the process and these achievements are at risk of being taken for granted or lost in the flow of history. Documenting the process, milestones, and key players provides insight and guidance for continuing to improve cancer care, advance research, and reduce cancer incidence and mortality. Cancer care is a microcosm of the larger healthcare system providing insight and lessons on the importance of developing and maintaining a research infrastructure and the role of multi-level collaboration and partnerships involving both the private and public sectors.