It is one of the four regional campuses which make up Palmetto College in the University of South Carolina System.

The college began holding classes in the Williams House in downtown Lancaster in September 1959, but by the mid-1960s growth forced it to find a larger facility.

With the support of the local community, the college moved to a tract of land on the northern limits of the City of Lancaster.

[1] Through Palmetto College and the entire USC system, an additional 24 online degree completion programs are offered including business, elementary education, public health, criminal justice, and hospitality.

USC Lancaster's athletic program is known as the Lancers, and their four teams compete in Region X of the NJCAA.