He became an editor of The Wilson Quarterly in 1977. From the mid 1970s until 2004 he worked with his father, John Cullen Murphy, as writer for the comic stripPrince Valiant, for which his father produced the artwork. He is also the author of The Word According to Eve: Women and the Bible in Ancient Times and Our Own (1999); Are We Rome? (2007), which compares the politics and culture of Ancient Rome with that of the contemporary United States; and God's Jury: The Inquisition and the Making of the Modern Word (2012).
He currently serves as editor at large for Vanity Fair and lives in Massachusetts. He is on the advisory board of the literary magazine The Common, based at Amherst College. He has three children: Jack, Anna, and Tim.