The first settlers came to Mecklenburg County in the late 1740s and were predominantly Scots-Irish Presbyterians from Pennsylvania, Maryland, and Virginia fleeing the Indian troubles in those colonies. They found the native Catawba Indians in this area friendly. Not long afterward, small groups of Germans and Swiss migrated here from the coast and other Scots-Irish came up from South Carolina.

The petition to form a new county was granted by the colonial Assembly on 11 December 1762. Mecklenburg County was formed on 1 February 1763 and named in honor of Queen Charlotte of Mecklenburg, consort of England’s King George III. It was bounded on the east by Anson County, on the north by Rowan County, on the south by South Carolina, and on the west by the Mississippi River. Until 1772, it included most of Union, all of Cabarrus, Lincoln, and Rutherford Counties in North Carolina, and all or part of York, Chester, Lancaster, Union, Spartanburg, Laurens, Cherokee, Kershaw, Newberry, and Greenville Counties in South Carolina. After several boundary line adjustments, Mecklenburg County assumed its present form in 1842 with a slight modification in 1889.

Until the early 1800s, the only church denomination in Mecklenburg County was Presbyterian. Sugar Creek Presbyterian Church was founded in 1755. Other Presbyterian churches were formed in various areas of the county: Steele Creek (1760), Hopewell (1762), Poplar Tent (1764), Centre (1765), Providence (1767), and Clear Creek, which was later named Philadelphia (1770).

Two presidents were born in old Mecklenburg: Andrew Jackson in 1767 and James K. Polk in 1792. In 1791, George Washington visited Charlotte.

The years 1781 to 1800 saw rebuilding and growth; several stores, a flour mill, and a saw mill were opened. A post office was established in 1792, and a stagecoach service was formed in 1794. Gold was discovered in 1800, and Charlotte was called the Gold Capital of the United States when the first branch of the U. S. Mint opened in 1837. In the 1850s railroads and the telegraph came to Mecklenburg, but the population in 1850 was less than it had been in 1830 due to heavy emigration to the South and West.

In 1861, the U. S. Mint was seized and converted to Confederate Headquarters for the area. The Confederate States Navy Yard was established in Charlotte, and in 1865 records of the State Department of the Confederacy and the Great Seal were stored in the Mecklenburg County Courthouse. Later that year the last full meeting of the Confederate Cabinet took place in Charlotte. Union troops occupied Charlotte from June 1865 until 1872.

Charlotte today is known as the Queen City, and from its historical roots as a manufacturing and agricultural center, it has become a major international center for banking and distribution.