The first European to visit Ohio was either Robert Cavelier, sieur de La Salle, or Louis Jolliet. La Salle explored the Ohio River area between 1669 and 1670, and Jolliet journeyed along Lake Erie. Led by Shawnee Chief Blue Jacket, remnants of the early Indian tribes were defeated at the Battle of Fallen Timbers in 1794. This U.S. Army victory led to the establishment of the Greenville Treaty Line in 1795, which separated the Indian land to the northwest from the settlers' land to the east and south.

The Ohio Country became part of the Northwest Territory in 1787. Connecticut and Virginia retained title to Ohio land, forming the Connecticut Western Reserve in the northeast and the Virginia Military District between the Little Miami and Scioto Rivers in the southwest. Ohio Company of Associates acquired 1,875 square miles in southeastern Ohio and in 1788 founded Ohio's first town, Marietta, at the confluence of the Ohio and Muskingum Rivers. Ohio entered the Union in 1803, with Edward Tiffin its first governor.