Upton studied history and English as a Phi Beta Kappa undergraduate at Colgate University from 1965 to 1970.
He earned an M.A. (1975) and Ph.D. (1980) in American Civilization at Brown University. His dissertation concerned seventeenth- and eighteenth-century domestic architecture in Tidewater Virginia, written under the supervision of James Deetz.
He taught for many years at UC Berkeley, before moving in 2002 to the University of Virginia, where he was David A. Harrison Professor of Anthropology and Architecture, with appointments in the School of Architecture and the department of anthropology. He resumed teaching at the University of California, Los Angeles as Professor of Architectural History and chair of the Department of Art History.
Upton authored the 1998 textbook ''Architecture in the United States'' for the Oxford University Press' Oxford Art History series and ''American Architecture, A Thematic History'' with Oxford in 2019. Upton has written extensively on vernacular landscapes of the American built environment. His work on Colonial and Antebellum America include ''Another City: Urban Life and Urban Spaces in the New American Republic'' (Yale University Press, 2008), ''Holy Things and Profane: Anglican Parish Churches in Colonial Virginia'' (MIT Press, 1986), ''Madaline: Love and Survival in Antebellum New Orleans'' (University of Georgia Press, 1996), and ''America’s Architectural Roots: Ethnic Groups That Built America'' (Preservation Press, 1986). As a founding member of the Vernacular Architecture Forum, Upton has published on materialist history and theory as separate from canonical architectural histories in works such as ''Common Places: Readings in American Vernacular Architecture'', with John Michael Vlach (University of Georgia Press, 1986) and "Architecture History or Landscape History?" in the ''Journal of the Society of Architectural Historians'' (August 1991). He wrote the chief essay for the Metropolitan Museum of Art's exhibition "''Art and the Empire City: New York 1825–1861'' in 2000. He examined histories of civic memorials in ''What Can and Can't Be Said: Race, Uplift, and Monument Building in the Contemporary South'' (Yale University Press, 2015).
