[5] It was named "Upper" because it is located near the headwaters of the Sandusky River, which flows into Lake Erie.

During the Crawford expedition of 1782, Pennsylvania militiamen sought to destroy the town after the Wyandot began killing American settlers in the region, but were defeated en route.

After the war, in September 1783, a number of Native Americans met at Upper Sandusky and formed the Western Confederacy, a confederation intended to resist U.S. expansion into the Northwest Territory.

In the War of 1812, the village became the site of Fort Feree (or Ferree) on a bluff overlooking the flood plain of the Sandusky River[7] The Fort was built in late 1812 by Pennsylvania militia led by Lieutenant Colonel Joel Ferree, by order of General William Henry Harrison.

Prior to that, it was in northwestern Ohio Indian country above the Greenville Treaty line of 1795.

Numerous indigenous Wyandot kept their settlements here until 1842, when they were driven out under the Indian Removal Act of 1830 to what became Wyandotte County, Kansas.

A small community of free Black people also lived in the old village.

A new town of Upper Sandusky was platted nearby the forcibly abandoned Wyandot village in 1843 and the first colonizer's house was built in 1845.

34.8% of all households were made up of individuals, and 17.1% had someone living alone who was 65 years of age or older.

[18] In 2023, it was discovered that Upper Sandusky was home to a group promulgating a White supremacy and Nazi homeschooling curriculum.