The Sandy Creek Expedition, with Maj. Andrew Lewis in command, was dispatched in February 1756 during the French and Indian War to attack the Shawnee villages in Ohio. At the time of the defeat of Gen. Edward Braddock's forces in July 1755, the Indians had rampaged through the forward settlements in the New, Greenbrier, and Tygart river valleys. Scores of settlers were killed, wounded, or captured, among whom were Mary Draper Ingles and Capt. Samuel Stalnaker, both of whom eventually escaped from the Shawnee villages. Many early settlers retreated across the Alleghenies or to the Shenandoah Valley.

Frontiersmen who remained behind demanded that Governor Robert Dinwiddie authorize a force of militia to punish the Shawnees. Several companies totaling more than 300 men, of whom nearly one-third were Cherokee Indians led by Ostenaco, left Fort Frederick on the New River near Ingles Ferry on February 18. William Ingles, husband of Mary Draper Ingles, was among them.

The expedition was doomed almost from the beginning due to harsh weather, swollen streams and rivers, and lack of provisions. They reached the headwaters of the Big Sandy River on February 28, and within a few days flour rations were cut by half. Game was scarce, and the men refused to slaughter and eat their horses and pack animals. In spite of Major Lewis's appeals and threats, fewer than 30 officers and men volunteered during a March 13 council to continue. The force returned to Fort Frederick, and the House of Burgesses subsequently cleared Lewis of any fault in the expedition's failure. Among the few benefits of the campaign were closer ties between the Virginia colonial government and the Cherokee Nation.