Rising obesity rates in the U.S. over the past several decades, particularly among children and adolescents, led to an increased focus on research addressing obesity prevention and public- and private-sector initiatives on healthy eating and physical activity. Groups conducting prevention initiatives recognized that their ability to achieve and sustain cross-sector environmental, policy, and systems-level solutions was hampered by limited evidence in those areas. In 2007, the Centers for Disease Control and Prevention, NIH, and the Robert Wood Johnson Foundation began to discuss forming a partnership that could accelerate progress to prevent childhood obesity by coordinating research and evaluation agendas and collaboratively building an evidence base. This paper describes the formation, structure, and operations of the National Collaborative on Childhood Obesity Research, the resulting partnership between the Centers for Disease Control and Prevention, NIH, the Robert Wood Johnson Foundation, and since 2010, the U.S. Department of Agriculture. It includes a discussion of lessons learned from, and benefits of, this collaborative model.