The first Europeans to enter what is now Rowan County were members of the Spanish expedition of Juan Pardo in 1567. They established a fort and a mission in the native village of Guatari, believed to be located near the Yadkin River and inhabited by the Wateree. At the time, the area was ruled by a female chief whom the Spaniards called Guatari Mico (Mico was a term common among the Muskogee and Souian speaking peoples of the south to mean "chief" or "leader"). The Spaniards called the village Salamanca in honor of the city of Salamanca in western Spain, and established a mission, headed by a secular priest named Sebastián Montero.
This fort was one of six that Pardo's expedition established before he returned separately to Spain in 1568. Small garrisons were stationed at each fort. They were built into the interior, including across the mountains in what is now southeastern Tennessee. In 1568, Native Americans at each fort massacred all but one soldier in the garrisons. The Spanish never returned to this interior area in other colonizing attempts, instead concentrating their efforts in Spanish Florida.
English colonial settlement of North Carolina came decades later, starting in the coastal areas, where settlers migrated south from Virginia. Explorers and fur traders were the first to reach the Piedmont, paving the way for eventual settlers. Rowan County and St. Luke's Parish were established on March 27, 1753, from the upper part of Anson County, North Carolina. It was named for Matthew Rowan, acting governor of North Carolina from 1753 to 1754. It was intended to incorporate all of the lands of the Granville District that had previously been included in Anson County.
A house several miles west of present-day Salisbury in "the Irish settlement" served as the first courthouse starting June 15, 1753. Daniel Boone's father Squire Boone served as one of the first magistrates. By mid-1754 a new courthouse site was selected near "the place where the Old Waggon Road (crosses) over Grant's Creek."