The county was formed in 1779 from Guilford County. It was named for Peyton Randolph, first president of the Continental Congress.
Some of the first settlers of what would become the county were English Quakers, who settled along the Haw River, Deep River, and Eno River.
Randolph County was the original location of what became Duke University.
The county is home to one of the last remaining covered bridges in the state. The Pisgah Covered Bridge, in Union Township, is in the southwestern part of the county and was destroyed by a flood in 2003, but has been completely restored and is still standing.