Bertram Wyatt-Brown was born in Harrisburg, Pennsylvania on March 19, 1932. He is the son of Laura H. and Episcopal bishop Hunter Wyatt-Brown. Following his high school education, Wyatt-Brown matriculated at the University of the South, earning his B.A. there in 1953. He joined the Armed Services from 1953 to 1955, becoming a lieutenant junior grade in the Naval Reserve. After his military service, he received a second B.A. degree from King's College at Cambridge University in 1957. Wyatt-Brown earned his Ph.D. in history at Johns Hopkins University in 1963. While at Johns Hopkins, he met and married Anne Jewett Marbury. The couple has two daughters, Laura and Natalie.

After completing his doctorate, Bertram Wyatt-Brown embarked on a series of academic appointments with growing security and prestige. He began with two year appointments at Colorado State University and the University of Colorado at Boulder. He then taught at Case Western Reserve University in Cleveland for 17 years, attaining the rank of full professor. At Case Western, Wyatt-Brown began his esteemed publishing career with 1969's Lewis Tappan and the Evangelical War Against Slavery. In 1974, he won a prestigious Guggenheim Fellowship.

His most esteemed book has been 1982's Southern Honor: Ethics and Behavior in the Old South. David Herbert Donald, himself an esteemed historian of the American South, wrote in the New York Times Book Review that "Mr. Wyatt-Brown's remarkable book...is not a tissue of generalizations but a tapestry of hundreds of specific illustrations drawn from every conceivable collection of Southern manuscripts and newspapers" though he was much less approving of the anthropological tone in writing style and the numbers of refinements and comparisons to other societies. Nonetheless this book that argues the centrality of "honor" to an understanding of Southern society was a finalist for both the American Book Award and for the Pulitzer Prize.

Wyatt-Brown would continue writing histories of Southern culture and Southern families during his tenure at the University of Florida, where he held the Richard J. Milbauer Chair in History. In 1994 he was President of the Society of Historians of the Early American Republic and in 2000-01 he was President of the Southern Historical Association. In 1998 he was awarded a fellowship from National Endowment for the Humanities.

Bertram Wyatt-Brown retired at the rank of Professor Emeritus from the University of Florida at the end of the 2003-2004 academic year. Later that year the proceedings of a conference on the Civil War that he and Peter Wallenstein edited were published by the University of Virginia Press. In October 2005, the University of Florida sponsored a conference honoring Wyatt-Brown called "Honoring a Master" at which numerous historians gave papers. Since retirement, Wyatt-Brown has served in named academic chairs at the University of Richmond and at the College of William and Mary and has been working on the draft of a book entitled Honor and America's Wars: From the Revolution to Iraq, as well as books on the aftermath of Lincoln's assassination and the trope of depression in Southern writing. Wyatt-Brown and his wife Anne continue to live in the Gainesville area, but keep active with writing and speaking engagements with the Organization of American Historians.