The first people in Ohio, some 11,000 years ago, were hunters. Their stone tools have been found with skeletal remains of long-extinct mammoths and mastodons. Centuries later, Ohio was inhabited by the Adena people, the earliest mound builders. Their descendants, the Hopewell Indians, built burial mounds, fortifications, and ceremonial earthworks, some of which are now preserved in state parks.

The first European travelers in Ohio, during the 17th century, found four Indian tribes: Wyandot and Delaware in northern Ohio, Miami and Shawnee in the south. All were hunters who followed game trails that threaded the dense Ohio forest. All together, these four tribes numbered about 15,000 people. European exploration was begun by a French nobleman, Robert Cavelier, Sieur de la Salle, who, with Indian guides and paddlers, voyaged from the St. Lawrence River to the Ohio, which he explored in 1669–70. In the early 1700s, French and English traders brought knives, hatchets, guns, blankets, tobacco, rum, and brandy to exchange for the Indians' deer and beaver skins.

Both the French and the English claimed possession of Ohio, the French claim resting on La Salle's exploration, while the British claimed all territory extending westward from their coastal colonies. To reinforce the French claim, Celeron de Bienville led an expedition from Canada to Ohio in 1749 to warn off English traders, win over the Indians, and assert French possession of the land. Traveling by canoe, with marches overland, he found the Indians better disposed at that time to the English than to the French. The following year, a company of Virginia merchants sent Christopher Gist to map Ohio trade routes and to make friendship and trade agreements with the tribes. The clash of ambitions brought on the French and Indian War—during which the Indians fought on both sides—ending in 1763 with French defeat and the ceding of the vast western territory to the British. During the Revolutionary War, the American militiaman George Rogers Clark, with a small company of woodsmen-soldiers, seized British posts and trading stations in Ohio, and, in the Battle of Piqua, defeated Indian warriors allied with the British. It was largely Clark's campaigns that won the Northwest Territory for the US.

The new nation had a huge public domain, extending from the Allegheny Mountains to the Mississippi River. To provide future government and development of the territory northwest of the Ohio River, the US Congress enacted the Land Ordinance of 1785 and the Northwest Ordinance of 1787. The Land Ordinance created a survey system of rectangular sections and townships, a system begun in Ohio and extended to all new areas in the expanding nation. The farsighted Northwest Ordinance provided a system of government under which territories could achieve statehood on a basis equal with that of the original colonies. When a specified area had a population of 60,000 free adult males, it could seek admission to the Union as a state.

The first permanent settlement in Ohio was made in 1788 by an organization of Revolutionary War veterans who had received land warrants as a reward for their military service. They trekked by ox-drawn wagons over the mountains and by flatboat down the Ohio River to the mouth of the Muskingum, where they built the historic town of Marietta. John Cleves Symes, a New Jersey official, brought pioneer settlers to his Miami Purchase in southwestern Ohio; their first settlement, in 1789, eventually became the city of Cincinnati. Access to the fertile Ohio Valley was provided by the westward-flowing Ohio River, which carried pioneer settlers and frontier commerce. Flatboats made a oneway journey, as families floated toward what they hoped would be new settlements. Keelboats traveled both downstream and upstream—an easy journey followed by a hard one. The keelboat trade, carrying military supplies and frontier produce, created an enduring river lore. Its legendary hero is burly, blustering Mike Fink, "half horse and half alligator," always ready for a fight or a frolic, for riot or rampage.

Increasing settlement of the Ohio Valley aroused Indian resistance. War parties raided outlying villages, burned houses, and drove families away. Two military expeditions against the Indians were shattered by Chief Little Turtle and his Miami warriors. Then, in 1793, Maj. Gen. "Mad Anthony" Wayne took command in the west. He built roads and forts in the Miami Valley, and trained a force of riflemen. On a summer morning in 1794, Wayne routed allied tribesmen, mostly Miami and Shawnee, in the decisive Battle of Fallen Timbers. In the ensuing Treaty of Greenville, Indian leaders surrendered claim to the southern half of Ohio, opening that large domain to uncontested American occupation.

When, in 1800, Connecticut ceded to the US a strip of land along Lake Erie claimed by its colonial charter and called the Western Reserve, that region became a part of the Northwest Territory. Now the future seemed unclouded, and from the older colonies came a great migration to the promised land. By 1802, Ohio had enough population to seek statehood, and in November, a constitutional convention assembled at Chillicothe. In 25 days and at a total cost of $5,000, the 35 delegates framed a constitution that vested most authority in the state legislature and gave the vote to all white male taxpayers. On 1 March 1803, Ohio joined the Union as the 17th state.

Beyond Ohio's western border, Indians still roamed free. In 1811, the powerful Shawnee chief Tecumseh led a tribal resistance movement (supported by the British) seeking to halt the white man's advance into the new territory and to regain lands already lost to the Americans. Ohio militia regiments led by Gen. William Henry Harrison repulsed an Indian invasion near Toledo in the battle of Tippecanoe on 7 November 1811. Control of Lake Erie and of Great Lakes commerce was at stake when Commodore Oliver Hazard Perry won a decisive naval victory over a British fleet in western Lake Erie during the War of 1812. Tecumseh was slain in the Battle of Thames in Canada on 5 October 1813.

With peace restored in 1815, "Ohio fever" spread through New England. In a great migration, people streamed over the mountains and the lakes to a land of rich soil, mild climate, and beckoning opportunities. Across the Atlantic, especially in England, Ireland, and Germany, thousands of immigrants boarded ship for America. At newly opened land offices, public land was sold at $1.25 an acre. Forest became fields, fields became villages and towns, towns became cities. By 1850, Ohio was the 3rd most populous state in the Union.

Having cleared millions of acres of forest, Ohioans turned to economic development. Producing more than its people consumed, the state needed transportation routes to eastern markets. The National Road extended across the central counties in the 1830s, carrying stagecoach passengers and wagon commerce from Pennsylvania and Maryland. The Ohio canal system, created between 1825 and 1841, linked the Ohio River and Lake Erie, providing a waterway to the Atlantic via New York's Erie Canal. In 1826, state lands were valued at $16 million; 15 years later, their value exceeded $100 million. The chief products were wheat, corn, pork, beef, salt, wool, and leather. By 1850, when farm and factory production outstripped the capacity of mule teams and canal barges, railroad building had begun. In the next decade, railroads crisscrossed the state.

In 1861, Ohio, like the rest of the nation, was divided. The northern counties, teeming with former New Englanders, were imbued with abolitionist zeal. But Ohio's southern counties had close ties with Virginia and Kentucky across the river. From southeastern Ohio came Clement L. Vallandigham, leader of the Peace Democrats—called Copperheads by their opponents—who defended states' rights, opposed all of President Lincoln's policies, and urged compromise with the Confederacy. While Ohio surpassed its quota by providing a total of 320,000 Union Army volunteers, the Copperhead movement grew strong enough to nominate Vallandigham for state governor in 1863. Responding to the news of Vallandigham's defeat by the rugged Unionist John Brough, Lincoln telegraphed: "Ohio has saved the nation." Ohio became directly involved in the war for two weeks in 1863, when Confederate Gen. John Hunt Morgan led a Kentucky cavalry force on a daring but ineffectual raid through the southern counties.

Ohio gave the Union its greatest generals—Ulysses S. Grant, William Tecumseh Sherman, and Philip H. Sheridan—each of whom won decisive victories at crucial times. Also essential to the Union cause was the service of Ohio men in Lincoln's cabinet, including Treasury Secretary Salmon P. Chase and War Secretary Edwin M. Stanton.

Mid-19th-century Ohio was primarily an agricultural state, but war demands stimulated Ohio manufacturing, and in the decade following the war, the state's industrial products surpassed the value of its rich farm production. The greatest commercial development came in northern Ohio, where heavy industry grew dramatically. To Toledo, Cleveland, and Youngstown via Lake Superior came iron ore that was converted into iron and steel with coal from the Ohio Valley. In the 1870s, John D. Rockefeller of Cleveland organized the Standard Oil Co., which soon controlled oil refining and distribution throughout the nation. At the same time, B. F. Goodrich of Akron began making fire hose, the first rubber product in an industry whose prodigious growth would make Akron the "rubber capital of the world." In the middle of the state, the capital city, Columbus, became a center of the brewing, railroad equipment, and farm implement industries. Cincinnati factories made steamboat boilers, machine tools, meat products, railroad cars, and soap. Dayton became known for its paper products, refrigerators, and cash registers. With industrial growth came political power. In the next half century, Ohio virtually took possession of the White House. Presidents Grant, Rutherford B. Hayes, James A. Garfield, Benjamin Harrison, William McKinley, William Howard Taft, and Warren G. Harding were all Ohioans.

The four great business pursuits—agriculture, commerce, mining, and manufacturing—were remarkably balanced in Ohio. Its ethnic strains were various. Following the earlier English, Irish, and German influx came Italian, Czech, Dutch, Finnish, Greek, Hungarian, Polish, Russian, Serbian, and Ukrainian immigrants, along with a growing number of blacks from the rural South. Thus Ohio provided an advantageous background for a president; to any segment of the nation, an Ohio candidate did not seem alien. In the 1920 campaign, both the Republican and Democratic nominees—Harding and James M. Cox—were Ohio men. Norman Thomas, a perennial Socialist candidate, was likewise an Ohioan.

During World War I, Ohio's heavy industry expanded and its cities grew. Progressivism developed in Toledo and Cleveland, under their respective mayors, Samuel M. "Golden Rule" Jones and Tom L. Johnson, whose reforms resulted in the city-manager form of government that spread to other Ohio cities. In the postwar 1920s, Ohio's oil, rubber, and glass industries kept pace with accelerating automobile production. Yet none of these industries was immune to the prolonged depression of the 1930s. Widespread unemployment and a stagnant economy were not relieved until the outbreak of World War II. The war swept 641,000 Ohioans into military service and gave Ohio industry military contracts totaling $18 billion.

The state's economy prospered after World War II, with highway building, truck and tractor production, aircraft manufacture, and airport construction leading the field. The completion of the St. Lawrence Seaway in 1959 made active international ports of Toledo and Cleveland. Major problems during this period involved pollution created by the dumping of industrial wastes (especially in Lake Erie) and urban decay resulting from the departure of middle-class families to the suburbs, an exodus that left the central cities to growing numbers of the poor and underprivileged. Related to these problems were troubles in the Ohio school system. Deteriorating neighborhoods produced inadequate revenues for schools and public services, and attempts at racial integration brought controversy and disturbance. When political offices were won by minority leaders—in 1967, for example, Carl Stokes of Cleveland became the first black mayor of any major US city—friction and tension continued. A further shock to Ohioans was the May 1970 shooting of 13 Kent State University students, four of whom died, by national guardsmen who had been sent to the campus to preserve order during a series of demonstrations against US involvement in Indochina (Vietnam).

During the early 1980s, Ohio was still beset by serious social and economic problems. While the state's population remained static, the unemployment rate in 1982 and 1983 reached 14%. A decline in manufacturing jobs was only partly offset by the employment brought by a growing service sector. In 1983, the state established the Thomas Edison Program to provide start-up companies with venture capital funds. The legislation helped jumpstart the state's economy. But by the end of the 1980s, economic progress slowed again. Unemployment rose in the recession of the early 1990s, reaching 6.9% in 1992. Within two years, as part of a national recovery, it had rebounded to 4.9%. In March 1995, Ohio was the site of the largest work stoppage in the auto industry in a quarter century, when almost 178,000 employees were laid off in response to a 17-day strike by auto workers at two General Motors plants in Dayton. In 1999 the economy was holding steady with an unemployment rate of 4.3%, in line with the national average. In July 2003, the unemployment rate stood at 6.2%, again on par with the national average. Ohio, like the rest of the nation, was experiencing heavy job losses due to a weak economy just beginning to recover from the 2001 recession.

Hunger and homelessness were on the rise in the late 1990s and early 2000s. A 1999 report by the Ohio Hunger Task Force found that nearly one million children in low-income family faced hunger, while the Coalition on Homelessness and Housing reported that need for emergency shelters for families had grown, stretching resources in the state's 10 largest counties.

In January 1999, newly elected Governor Robert Taft, the great grandson of President William Howard Taft, took office. His administration moved quickly to address the problem highlighted in a 1996 federal study that revealed the state had the worst school facilities in the nation. His plan to spend $23 billion on school repairs over 12 years was boosted in November 1999 by voters who approved Issue 1, a ballot initiative allowing Ohio to borrow money less expensively for school construction. The governor was also pushing for tougher gun control.

Conservancy programs at the state level encompassed the watersheds of the Muskingum and Miami rivers, which became models for such undertakings in other states in the 1980s. Pollution in Lake Erie, where poor water conditions had made national headlines, was successfully reversed through a coalition of government efforts. By the end of the 1990s, the state was viewed as a national leader in improving waterways. But, as the Environmental Protection Agency lined up partners to clean up the Cuyahoga River, Ohio still faced serious environmental threats. A study released in 2000 indicated air pollution in the Ohio River Valley was worse than that on the nation's East Coast. It was reported earlier that rain contaminated with mercury from coal-fired electric plants was polluting Midwest lakes and rivers. In 2000 the EPA released a study citing the state for failing to meet tighter federal ozone limits. Illegal dumping also posed a persistent problem, with an estimated 30 to 40 million tires having been unlawfully deposited at nearly 100 sites around the state.

In 2000 the state remained among the most populous in the nation, with its more than 11.3 million people giving it a rank of 7th among the states.

Ohio was one of the states affected by the 14 August 2003 massive power blackout in Canada, the Northeast, and Midwestern states. The largest electrical outage in US history affected 9,300 square miles and a population of over 50 million. An initial power failure in Ohio was later found to be the trigger for the outage. Many areas of Cleveland were without safe drinking water for a number of days.