Ostenaco (about 1703-1780) was an Overhill Cherokee leader active on the Virginia frontier in the pre-Revolutionary period. Born in present Tennessee, he had reached the rank of Outacite (Man Killer—the second highest rank in the Cherokee military system, equivalent to a colonel in the British system) by the beginning of the French and Indian War. His service during that war earned him the highest Cherokee rank, Skyagunsta, and a captain's commission in the Virginia colonial army.

Ostenaco served the Cherokee-British alliance in Western Virginia in 1756, 1757 and 1758, traveling over 3,500 miles on foot and by canoe. On Andrew Lewis's ill-fated Sandy Creek Expedition in 1756, Ostenaco led 130 Cherokees, with Round O and Yellow Bird also serving as officers. He led his war party to what is now West Virginia's Eastern Panhandle in 1757. Stationed at Pearsall's Fort (Romney), his war party raided the French stronghold at Fort Duquesne (present Pittsburgh). In 1758, three Cherokee leaders operated a pincer campaign against Fort Duquesne. Ostenaco and Oconostota marched their warriors up the Ohio Valley to approach the fort from the west, while Round O approached from the east. This raid was one of many successful attacks by Cherokees and Catawbas against the French and their northern American Indian allies in 1758, which contributed to the French decision to withdraw from the Ohio Valley.

The military successes in which Ostenaco played a major role bolstered the Cherokee claim to ownership of land south of Ohio River and west of Kanawha River, and gave the Cherokee Nation an effective bargaining stance when the southwestern Virginia lands were considered during negotiations leading to the 1768 Treaty of Hard Labor. Ostenaco remained loyal to the British during the American Revolution, although he saw no military action due to his advanced age. He died in eastern Tennessee in 1780.