The now-submerged Icehouse Bottom site was occupied by indigenous cultures in the region as early as 7500 B.C.

This area was part of the homelands of the historic Cherokee people, which extended into western Virginia, North and South Carolina, and northeastern Georgia, long before these colonies or states were founded.

By the time Euro-American explorers arrived in the area in the 18th century, the Cherokee had established several towns along the Little Tennessee.

They included Tanasi, the name source for the state of Tennessee, Chilowhee, and Chota, the "mother town" of the Overhill Cherokee in the mid to late 18th century.

The English traders and colonists referred to these places as the Overhill Towns, because they crossed the Appalachian Mountains from the east to reach them.

Cherokee chief Dragging Canoe came from Mialoquo, which was located just north of the site of the modern US-411 bridge.

Tuskegee, which developed adjacent to Fort Loudoun, was the birthplace of Sequoyah (c. 1770–1843), creator of the written Cherokee syllabary.

The Tellico agent, the chief American diplomat to the Cherokee, operated out of the blockhouse and ran a trading post there for a decade.

In 1819, the Cherokee signed the Calhoun Treaty, ceding what is now Monroe County to the United States.

Niles Ferry, the primary crossing of the Little Tennessee River along the Old Federal Road (the predecessor of US-411), was established in 1805 by early settler Barclay McGhee.

Three years later, area doctor Walter Kennedy applied for a post office for Upton Station.

When the US postal service informed him that the name of Upton Station had been taken, Kennedy chose the name "Vonore", a combination of the German word von (meaning "of") and the English word "ore", as Kennedy believed the town would become a mining town.

In the 21st century, it includes many older houses, the library, the town hall, and other municipal buildings.

Archaeological surveys and excavations were undertaken along the Little Tennessee River prior to flooding in order to salvage artifacts from known pre-historic and historic sites, including the Cherokee town sites of Tanasi and Chota, and the early US federal period Tellico Blockhouse.

An area was raised above the water level, and posts and fill were place in order to show visitors its layout on the historic site.

The eastern portion extends into Blount County along Ninemile Creek and around the Ft Loudon State Park.

Tennessee State Route 72 connects the town with Tellico Village, Loudon, and Interstate 75 to the north.