At the time the English began settling Virginia in the 1600s, the inhabitants of what is now Nelson County were members of a Siouan-speaking tribe, the Nahyssan.

On the night of August 19–20, 1969, Nelson County was struck by disastrous flooding caused by Hurricane Camille.

The hurricane hit the Gulf Coast two days earlier, weakened over land, and stalled on the eastern side of the Blue Ridge Mountains, dumping a world-record quantity of 27 inches (690 mm) of rain, mainly in a three-hour period.

There were reports of animals drowning in trees and people who had had to cup their hands around their mouth and nose to breathe.

[5] Flash floods and mudslides killed 153 people, 31 from Roseland, Tyro, and Massies Mill alone.

[7] In the tiny community of Davis Creek, 52 people were killed or could not be found; only 3 of 35 homes were left standing after the floodwaters receded.

[6] The bodies of some people have never been found; others washed as much as 25 miles (40 km) downstream along the creeks and rivers.

There was severe flooding elsewhere in Virginia, such as along the Maury River, which destroyed the town of Glasgow in Rockbridge County.

The James River and its tributaries normally drain Nelson County, but in the face of unusually high flooding from other tributaries such as Hatt Creek (along the James River some 80 miles (130 km) to the east) the James River crested more than 20 feet (6.1 m) above flood stage at Westham, as Nelson County citizens watched portions of houses and other buildings, bodies, and dead livestock flow past.

Visitors to Nelson County can participate on a self-guided tour of notable locations related to Hurricane Camille.

Nelsonite is a distinctive igneous rock composed primarily of the minerals ilmenite and apatite, and as such it's rich in both titanium and calcium phosphate.

A planned development begun in 1969, it offers 45 holes of championship golf, seasonal skiing, snowboarding and snowtubing.

Abandoned during World War II and converted to a foot/bike trail in the 2020s, a walk through the tunnel is about 2.5 miles long.

[20] The first annual Lockn' Music Festival was held September 5–8, 2013 on a farm in Nelson County near Arrington, Virginia.

[21] Camp Jeep was held at the Oak Ridge Estate in Arrington for several years beginning in 1999, with the last event taking place in 2007.

The last time any candidate exceeded 55% of the vote was in 1984, when Ronald Reagan carried the county in his 49-state landslide.