His most famous work, Bury My Heart at Wounded Knee (1970), details the history of the United States' westward colonization of the continent between 1860 and 1890 from the point of view of Native Americans.

He spent much time in the public library reading the three-volume History of the Expedition under the Command of Captains Lewis and Clark which saw him develop an interest in the American West.

[1] While attending home games by the baseball team the Arkansas Travelers, he became acquainted with Chief Yellow Horse, a pitcher.

Brown worked part-time for J. Willard Marriott, attended classes, and married Sally Stroud (another graduate of Arkansas State Teachers College drawn to Washington by the New Deal).

From 1948 to 1972, he was an agriculture librarian at the University of Illinois at Urbana–Champaign, where he had gained a master's degree in library science, became a professor, and raised a son, Mitchell, and daughter, Linda, with his wife Sally.

During the 1960s, he completed eight more including The Galvanized Yankees, which Brown described as requiring more research than any of his other books, and The Year of the Century: 1876, which he described as his personal favorite.