René Robert Cavelier, Sieur de la Salle, the French explorer, traveled through Ohio land in 1667 and is thought to have been the first white person to see the Ohio River. Eighty years later, in 1747, the Ohio Company of Virginia was organized to colonize the Ohio River Valley, leading to the creation of the Ohio Land Company two years later. Great Britain gained control of the region following the French and Indian War in 1763 but lost it again in 1779.

The establishment of Northwest Territory in 1787 marked the beginning of a steady stream of migration. Scots-Irish from Virginia, Kentucky, and Ohio settled mainly in Marietta in Washington County. New Englanders and Revolutionary War soldiers, most of them from Massachusetts and Ohio, arrived in that same area followed by Essex County, New Jersey, people, who settled in Cincinnati in an area called the Symmes Purchase. French immigrants settled in Gallipolis, Gallia County, from 1790 through 1791. Additional Ohio migrations occurred in 1796-97, settling in the Ohio Western Reserve. Others from Ohio and Vermont settled in what became Geauga County three years later. Clermont County was the new home of those from Maine in 1796, the same year that emigrants from Scotland arrived in Montgomery County. In 1796 the Refugee Tract was established in Columbus for Canadians who sympathized with the American Revolution. Three years later Ohio Territory was created, followed in 1800 by the first Ohio territorial census and the opening of the first land offices at Marietta, Steubenville, Chillicothe, and Cincinnati. The territory became a state in 1803.

The influx of new settlers continued, with Germans and Welsh from Ohio, plus additional migrations from Kentucky and Virginia. Statehood was rapidly achieved in 1803. Three years later the United Society of Believers of Christ's Second Appearing (Shakers) migrated to Warren County. Germans settled in Brown and Tuscarawas counties from 1814 through 1824. The opening of the Erie Canal in 1825 was an opportunity for those in the northeastern United States to migrate to Ohio. The Mormons (see Church Records) arrived in Ohio in 1831. English and Irish emigrated to Ohio for railroad construction employment in the 1840s. By 1860, Ohio's extensive railroad construction provided more miles of track than any other state.

Ohio was intensely involved with the abolitionist movement prior to the Civil War having considerable activity in the Underground Railroad along Lake Erie and the Ohio River. Following the Civil War, the state gained national political power, producing seven United States presidents. As an agricultural and industrial state, some early industries were barrel-making and meat packing. The American Federation of Labor formed there in the 1880s. The industrialization and urbanization of Ohio brought new residents from eastern and southern Europe and blacks from southern states. Mining became increasingly important with products of coal, limestone, and salt.

Twelve to fifteen thousand native inhabitants were said to have been living in Ohio country when the first European settlers arrived. The Miami lived in the western part of Ohio, and the Wyandotte were in the northwest. The Huron, the Ottawa, and the Seneca were also in the northwest. The Shawnee tribe was located in the lower Scioto Valley, the Delaware in the Muskingum Valley, the Tuscarora in the northeastern section of that valley, and the Mingo occupied the east.

In the mid-1700s, the French and the English began their long struggle for possession of the region. The English victory was followed by the battles of the American Revolution; the native inhabitants of Ohio were tragically involved in both of these wars. When the bloodshed was over between the two European factions, the contest for the land began in earnest between white and native. By the end of the Revolutionary War, still unwilling to give up their domain, the natives struggled to maintain their lands for twelve long years. In the summer of 1794, at the battle at Fallen Timbers, Anthony Wayne and his well-trained troops totally defeated the Native Americans of Ohio. The following year, in August of 1795, a treaty was negotiated-the final step in taking away native home lands. The last group of Native Americans left northwestern Ohio in 1833.