He was born in Hope, Vermilion County, Illinois on September 10, 1885 to a country doctor and was raised on the family farm. He earned a bachelor of arts from the University of Illinois at Urbana-Champaign in 1907 and a doctorate from Columbia University in 1911 and continued to teach there until 1930. He was a world federalist and once said, "It is obvious that no difficulty in the way of world government can match the danger of a world without it". In 1939, he was awarded the Pulitzer Prize for Biography or Autobiography for Benjamin Franklin.
Van Doren's study The American Novel, published in 1921, is generally credited with helping to re-establish Herman Melville's critical status as first-rate literary master.