Cresap was the son of the celebrated pioneer Colonel Thomas Cresap (c. 1702–c. 1790). He spent part of his adult years in the Ohio Country as a trader and land developer. He led several raids against Indians whom he believed were hostile to white settlement. The war leader Logan (c. 1723?–1780), of the Mingo Indians, accused Cresap of murdering his family. In fact, the killings were almost certainly perpetrated by Daniel Greathouse, yet Cresap was immortalized in Logan's speech — quoted in Thomas Jefferson's Notes on the State of Virginia (1785) — as the murderer of Logan's family.