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Ohio has three distinct topographical regions: the foothills of the Allegheny Mountains in the eastern half of the state; the Erie lakeshore, extending for nearly three-fourths of the northern boundary; and the central plains in the western half of the state.

The Allegheny Plateau in eastern Ohio consists of rugged hills and steep valleys that recede gradually as the terrain sweeps westward toward the central plains. The highest point in the state is Campbell Hill (1,549 ft/472 m), located in Logan County about 50 mi (80 km) northwest of Columbus.

The Erie lakeshore, a band of level lowland that runs across the state to the northwestern corner on the Michigan boundary, is distinguished by sandy beaches. The central plains extend to the western boundary with Indiana. In the south, undulating hills decline in altitude as they reach the serpentine Ohio River, which forms the state's southern boundary with Kentucky and West Virginia. The state's lowest point is on the bands of the Ohio River in the southwest, where the altitude drops to 455 ft (139 m) above sea level.

Most of Ohio's 2,500 lakes are situated in the east, and nearly all are reservoirs backed up by river dams. The largest, Pymatuning Reservoir, on the Pennsylvania border, has an area of 14,650 acres (5,929 ha). Grand Lake (St. Mary's), located near the western border, covering 12,500 acres (5,059 ha), is the largest lake wholly within Ohio.

Ohio has two drainage basins separated by a low ridge extending from the northeast corner to about the middle of the western border with Indiana. North of the ridge, more than one-third of Ohio's area is drained by the Maumee, Portage, Sandusky, Cuyahoga, and Grand rivers into Lake Erie. South of the ridge, the remaining two-thirds of the state is drained mainly by the Muskingum, Hocking, Raccoon, Scioto, Little Miami, and Miami rivers into the Ohio River, which winds for about 450 mi (725 km) along the eastern and southern borders.

Ohio's bedrock of sandstone, shale, and limestone was formed during the Paleozoic era some 300–600 million years ago. The oldest limestone rocks are found in the Cincinnati anticline, a ridge of sedimentary rock layers about 3,000 ft (900 m) thick that extends from north to south in west-central Ohio. Inland seas filled and receded periodically to form salt and gypsum, also creating peat bogs that later were pressurized into the coal beds of southeastern Ohio. At the end of the Paleozoic era, the land in the eastern region uplifted to form a plateau that was later eroded by wind and water into hills and gorges.

About two million years ago, glaciers covering two-thirds of the state leveled the western region into plains and deposited fertile limestone topsoil. As the glaciers retreated, the melting ice formed a vast lake, which overflowed southward into the channels that became the Ohio River. Perhaps 15,000 years ago, during the last Ice Age, the glacial waters ran off and reduced Lake Erie to its present size. Limestone rocks in Glacier Grooves State Park on Kelley's Island bear the marks of the glaciers' movements.