The Boones, English Quakers, left Pennsylvania in 1750 and settled (1751 or 1752) in the Yadkin valley of North Carolina. Daniel served as a wagoner in Braddock's ill-fated expedition (1755) against Fort Duquesne (Pittsburgh) and almost certainly took part in Gen. John Forbes's successful march on the same place in 1758. He became interested in Florida, but his wife, the former Rebecca Bryan, whom he married in 1756, refused to accompany him. He explored (1769–71) the Kentucky region thoroughly, and its prospects delighted him.

Attacks by Native Americans turned back his first colonizing attempt (1773), but in Mar., 1775, as advance agent for Richard Henderson and the Transylvania Company and with an armed band of 30 men, he blazed the famous Wilderness Road and founded Boonesboro (or Boonesborough) on the Kentucky River. Henderson arrived in a few weeks with additional settlers, and later in the same season Boone guided a second party, including his family. When Kentucky was made a county of Virginia in 1776, he was elected a captain of militia.

In the American Revolution, while on an expedition to find salt in the Blue Licks on the Licking River, Boone and his party were captured (Feb., 1778) by Shawnee and taken to British headquarters at Detroit. Highly regarded by his captors, he was adopted as a member of the tribe. He led them to think that he would prevail on the other settlers to surrender, but, after four months of captivity, he escaped in time to prepare Boonesboro for an attack by the tribe, which then failed. A disgruntled element charged Boone with disloyalty, and although he was promptly acquitted and elected major, he left Boonesboro and, after collecting his family, which had returned to North Carolina after his capture, founded (1779) a new settlement, Boone's Station, near what is now Athens, Ky.

Boone served several terms as representative in the Virginia legislature. His titles to large tracts of land were adjudged imperfect, and despite his services to Kentucky he lost his best holdings through ejectment suits. Disgusted, he and Rebecca followed (1799) a son to Missouri, where the Spanish government granted him a large tract in the Femme Osage valley and made him district magistrate. When the United States assumed jurisdiction over this territory after the Louisiana Purchase (1803), his land titles were again found to be defective, but the direct intercession of Congress (1814) restored part of his acreage.

Boone's adventures became well known through the so-called autobiographical account that appeared in the widely read Discovery, Settlement, and Present State of Kentucke (1784), by John Filson, and Lord Byron's verses on him in Don Juan gave his name international prominence. Historical scholarship has disproved many of the legends about him; nevertheless these still attest to those qualities of courage and determination that earned him enduring popularity.