Vance County High School was built in 1968 on Warrenton Road and was originally designed to serve students who lived in Vance County outside of the city of Henderson. However, the school first served students from the city of Henderson during the 1968-1969 school year after a fire destroyed portions of Henderson High School. In the 1971-1972 school year, the school became Vance Senior High School (grades 10-12) with students from across the county including those who had attended Henderson High School and Vance County High School. Two additional classroom wings were added to the school structure during the 1970s. The school continued to serve students as the county's only high school until 1990, with its enrollment reaching approximately 1,700 in the late 1980s. In the 1990-1991 school year, a second high school (Southern Vance) opened its doors, dividing the county's high school population (grades 9-12) among two schools. With the opening of the new high school, Vance Senior High became Northern Vance High School serving students who live in the northern and western portions of Vance County.

The first principal of the school was Edwin O. Young Jr. (the namesake of E.O. Young Jr. Elementary School). Young served as principal until 1976. He was succeeded as principal by Fred Owen, who served as the school's leader through the 1987-1988 school year. Wayne Adcock, who later became superintendent, was the principal at Vance Senior High beginning in 1988 and continued as the school's principal when it became Northern Vance High School. He left the principal's position in 1995, shortly before becoming superintendent. Adcock was succeeded by Charles Watson, who served as principal until the end of the 1997-1998 school year. Eric Pierce was named principal of Northern Vance High School for the 1998-1999 school year. Pierce served as principal of the school for six years. From 2004 to 2007, Hugh Brady was the principal of the school. He was followed by Brian Creasman, who became principal at the beginning of the 2007-2008 school year. Creasman continues to serve as the principal of Northern Vance High School.