James Thomas Flexner was born in Manhattan on January 13, 1908 to Simon and Helen (Thomas) Flexner. Simon Flexner (1863–1946), a physician, scientist, and professor of experimental pathology at the University of Pennsylvania, served as first director of the Rockefeller Institute for Medical Research. Helen (Thomas) Flexner (1871–1956), a professor of English at Bryn Mawr College (where her sister served as president), was connected by family marriages to the philosopher Bertrand Russell and the art critic Bernard Berenson.

As a child James Thomas Flexner found reading and writing difficult. He overcame his dyslexia one day as he sat in Central Park staring at a page of Beatrix Potter's The Tale of Peter Rabbit, when the printed marks suddenly formed themselves into words. This achievement so inspired Flexner that from then on writing his own stories became the focus of his life. Educated at the progressive Lincoln School of Columbia University's Teachers College, he went on to graduate magna cum laude with a degree in English from Harvard University in 1929. Soon after he was hired to write human interest pieces for the New York Herald Tribune, but left by 1931 for a position with the New York City Department of Health. He resigned the following year to devote his full time to writing.

His first book, Doctors on Horseback: Pioneers of American Medicine (1937), was inspired by the work of his father. (Simon Flexner is probably best known for developing a serum treatment for spinal meningitis.) From medicine he gravitated to art history, with America's Old Masters: First Artists of the New World (1939), a study of the painters Benjamin West, John Singleton Copley, Charles Willson Peale, and Gilbert Stuart. This work, and Flexner's three-volume History of American Painting (1947–1962), helped establish the subject as an academic specialty, despite the author's lack of formal training in the field.

American history and biography, too, supplied compelling material for Flexner's talents. 1953 saw publication of The Traitor and the Spy: Benedict Arnold and John André. This was followed in 1959 by Mohawk Baronet: Sir William Johnson of New York. But George Washington would prove Flexner's most enduring and rewarding subject.

The four-volume George Washington: A Biography, appeared between 1965 and 1972. Critics hailed Flexner's portrait for demystifying Washington, for moving beyond "the marble image" and bringing the hero "down from Olympus." The final volume, Anguish and Farewell, 1793–1799, won the 1973 National Book Award for Biography and a special Pulitzer citation. In 1974 Flexner published a single volume abridgment of the series, Washington: The Indispensable Man. Flexner's Washington works were adapted as television miniseries in the mid-1980s starring Barry Bostwick as the first president.

Flexner's later biographies, The Young Hamilton (1978) and States Dyckman: American Loyalist (1980) were followed by volumes of a personal nature: An American Saga: The Story of Helen Thomas and Simon Flexner (1984) and Maverick's Progress (1996), an autobiography.

James Flexner married professional singer Beatrice Hudson (1919–1998) in 1950. The couple had one daughter, Helen. Flexner died, age 95, in Manhattan, on February 13, 2003.

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This note is based on Flexner's obituary in the New York Times, February 16, 2003 ("James Thomas Flexner, Washington Biographer, 95 Dies"), his entry in the Dictionary of Art Historians, and information from his autobiography, Maverick's Progress (1996).