Duncan graduated from the New College of Florida in 1995 with a BA in Chemistry, and obtained his PhD in 2001 for work in the field of Inorganic Chemistry at Caltech. In 2001, he changed research fields to undertake postdoctoral studies in genetics and genomics at the Whitehead Institute at MIT, where he developed and deployed new methods in transcriptional regulation. His first major work as a postdoctoral fellow showed that primary human tissue can be used to map where diabetes-linked transcription factors bind the human genome in liver and pancreatic islets in vivo.

In 2006, he established his research group at the University of Cambridge. His independent research has focused on understanding how and why different species use highly conserved, tissue-specific transcriptional machinery in surprisingly different ways.

Duncan's appointment in 2011 at the Sanger Institute will allow his group to combine their comparative functional genomics approaches with the intellectual and research strengths of the other Sanger faculty in related areas.