James Gregory's research and teaching center on four aspects of 20th century United States history: (1) labor history, particularly the history of American radicalism; (2) regionalism, both the West and the South; (3) race and civil rights history; (4) migration, especially inside the United States.

He is the author of American Exodus: The Dust Bowl Migration and Okie Culture in California (Oxford, 1992), which was awarded the Ray Allen Billington Prize from the OAH and the Annual Book Award from the Pacific Coast Branch of the AHA. He is also the author of The Southern Diaspora: How the Great Migrations of Black and White Southerners Transformed America (University of North Carolina, 2005), which was the winner of the Philip Taft Labor History Book Prize. 

Much of his current work focuses on American social movements and the political geography of radicalism. The Mapping American Social Movements Project  produces and publishes interactive maps and visualizations about dozens of social movements that have influenced American life and politics during the 20th century, including radical political parties, Black freedom movements, Chicanx/Latinx movements, labor movements, women’s movements, antiwar and environmentalist movements, LGBTQ activism.