- First European settlement – 1526
Lucas Vasquez de Ayllon (c. 1475-1526) of Spain established San Miguel de Gualdape, probably near present-day Georgetown, but possibly further south. The settlement failed within a year due to famine, disease, and unrest in the black and American Indian populations ... leaving only 150 of the original 600 settlers to return to Santo Domingo.
- First slave revolt – November 1526
Black slaves revolted against Spanish settlers in San Miguel de Gualdape.
- First American-built ship to cross the Atlantic – 1563
A small group of French Huguenot settlers built a makeshift vessel and sailed from Port Royal for France after being left behind in Charlesfort by their leader, Jean Ribaut (c. 1520-1565).
- First public library – November 16, 1700
A law passed by the South Carolina General Assembly established a provincial library in Charles Town and provided for its governance. This library, located on St Philip's Street, remained in operation for 14 years.
- First professional female artist – 1707
Henrietta Dering Johnston (1670-1729) arrived in Charles Town in 1707. In addition to being the first professional female artist in the American colonies, Johnston was also the first artist in the colonies to work primarily with pastels.
- First opera performed – February 18, 1735
Colley Cibber's ballad opera Flora, or Hob in the Well, was performed at the Courtroom in Charles Town. The Courtroom was a large room in Shepard's Tavern that the provincial government rented for meetings of the court until the court house was built.
- First fire insurance company – February 3, 1736
The Friendly Society for the Mutual Insurance of Houses Against Fire was founded in Charles Town.
- First building constructed solely for use as a theater – February 12, 1736
The "new theatre in Dock Street" opened with a performance of George Farquhar's The Recruiting Officer. It is widely believed this building burned in the 1740 Charleston fire. Today's theater building, located on Church Street, opened as the Dock Street Theatre in 1937. It has the facade of the historic Planters' Hotel, which operated on the site for many years, while the interior is of modern construction with some period pieces from other Charleston sites.
- First systematic, scientific recording of weather information – April 1737
Dr. John Lining (1708-1760) took observations of Charles Town's weather three times a day from his home on Broad Street. He recorded temperature, rainfall, atmospheric pressure, humidity, wind direction, and wind speed.
- First major slave insurrection – September 9, 1739
After hearing a rumor that Spaniards were promising freedom to slaves in St Augustine, slaves from the Stono River plantations (southwest of Charleston) revolted. More than 20 whites and approximately 40 blacks died during the insurrection. "Stono's Rebellion" was the largest slave uprising in the British mainland colonies prior to the American Revolution.
- First musical society – 1762
The St Cecilia Society was founded in Charles Town.
- First cotton exported to England – 1764
The custom house in London, England recorded a shipment of 8 bales of cotton from Charles Town.
- First public museum – January 1773
A special committee of the Charlestown Library Society met to discuss the establishment of a museum in Charlestown. Several months later another committee was appointed by Lieutenant Governor William Bull II (1710-1791) to collect materials for the new Charleston Museum, which is now located on Meeting Street.
- First black Baptist Church – 1773
A Baptist Church for black slaves was founded in Silver Bluff, in present-day Aiken County. George Liele (1752-1825) was one of the church's early preachers.
- Oldest municipal Chamber of Commerce in continuous operation – December 9, 1773
The Charlestown Chamber of Commerce was organized at Mrs. Swallows Tavern on Broad Street. Today it is called the Charleston Metro Chamber of Commerce.
- First business publication – July 30, 1774
The earliest known edition of South-Carolina Price-Current listed prices for 168 things bought and sold in Charlestown.
- First independent government in the colonies – March 1776
Four months before the Declaration of Independence was signed, South Carolina adopted a state constitution–drafted by a Provincial Congress–and elected John Rutledge (1739-1800) as the state's president and Henry Laurens (1724-1792) as its vice-president. The titles of these offices were changed to Governor and Lieutenant Governor by the Constitution of 1778.
- First major naval battle of the Revolutionary War – June 28, 1776
Colonel William Moultrie (1730-1805) and his patriot troops defeated Sir Peter Parker's (1721-1811) attempt to sail a British Fleet into Charlestown harbor. The key to this critical American victory was a hastily constructed palmetto fort on the south end of Sullivan's Island. This structure was later named Fort Moultrie.
- First treaty between two US states – May 20, 1777
Georgia and South Carolina met with the Cherokee Indians to make the Treaty of DeWitt's Corner. South Carolina gained most of present-day Anderson, Oconee, Pickens, and Greenville counties through this treaty.
- First eminent architect born in America – 1781
Robert Mills (1781-1855), who designed many famous buildings and monuments, was born in Charlestown.
- First golf club – September 29, 1786
Scottish merchants formed the South Carolina Golf Club in Charleston. Club members played on Harleston Green in Charleston until 1800.
- First ice transported commercially – 1799
Ice was transported by ship from New York to Charleston.
- First tea planted – 1802
French botanist Francois Andre Michaux (1770-1855) planted tea at Middleton Barony (now known as Middleton Place) near Charleston.
- First fireproof building – 1823
Construction of Charleston's Fireproof Building began in 1823 and was completed four years later. This building, which is located at 100 Meeting Street, was designed by Robert Mills to house state records. The South Carolina Historical Society, which had offices in the building from 1859 until the end of the Civil War, has been located in the building since 1943.
- First Reform Jewish Congregation – November 21, 1824
The Reformed Society of Israelites was founded in Charleston by 47 members of Kahal Kadosh Beth Elohim after their petition to change the Sephardic Orthodox liturgy was denied.
- First regularly scheduled rail passenger service – December 25, 1830
The South Carolina Canal and Rail Road Company's Best Friend of Charleston made its first passenger run on Christmas Day. This new steam locomotive "flew" 141 brave souls along six miles of wood and metal rails at speeds of 15-25 miles an hour!
- First railroad junction – 1838
In 1833, the railroad from Charleston to Hamburg was completed, making it the longest railroad in the world at that time. (Hamburg was located in Aiken County but no longer exists.) Branchville was one of the stops along the way, and in 1838 a new line from Branchville to Columbia was completed, making Branchville the world's first railroad junction. The Branchville Railroad Museum now commemorates the town's long-standing railroad tradition.
- First municipal college – 1836
Although founded and chartered in the 18th century, The College of Charleston didn't come under municipal control until 1836.
- First trial in a worker's compensation lawsuit – July 1838
In the case of James Murray vs. South Carolina Railroad Company, the plaintiff was awarded a $1,500 verdict. This decision was later reversed by a higher court.
- First building to be used solely as a college library – May 6, 1840
Construction on the University of South Carolina's Library was completed in 1840 after a design by Robert Mills (1781-1855). The building served as USC's main library until 1940 and today it is home to the South Caroliniana Library.
- First patent for a mechanical refrigerator – May 6, 1851
Dr. John Gorrie (1803-1855), who was born in Charleston but spent his adult life in Florida, received a patent for a mechanical device capable of producing blocks of ice the size of bricks. Gorrie installed a mechanical refrigerator in the US Marine Hospital in Apalachicola.
- First state to secede – December 20, 1860
A state convention of 169 members met at St. Andrews Hall in Charleston and voted unanimously to secede from the Union. Convention members met in Institute Hall later that evening to sign the Ordinance of Secession.
- First shot fired in the Civil War – January 9, 1861
The US Vessel Star of the West was fired upon by Citadel Cadets stationed on Morris Island while trying to bring supplies to Fort Sumter.
- First black Civil War regiment – November 1862
A white Union officer, Colonel Thomas W. Higginson (1823-1911) of Massachusetts, mustered the First Regiment of South Carolina Volunteers into service.
- First black to earn a Medal of Honor – July 18, 1863
W. H. Carney (1840-1908) participated in the charge of the 54th Massachusetts against Battery Wagner.
- First submarine to sink a ship in battle – February 17, 1864
Confederate submarine H.L. Hunley sunk the USS Housatonic.
- First black state supreme court associate justice – February 1, 1870
Jonathan Jasper Wright (1840-1885) was elected to the South Carolina Supreme Court in 1870 and served until his resignation December 1, 1877.
- First commercial tea farm – 1890
Charles Shepard established a commercial tea farm in Summerville.
- First totally electric textile plant – 1893
Mount Vernon Mills opened in Columbia. The Columbia facility closed in 1980 and was donated to the state to house the South Carolina State Museum.
- First textile school established in a college – 1899
Clemson opened a textile department. In 1904 its first graduating class had 5 students.
- First rivetless cargo ship – February 1930
The Charleston Dry Dock and Machine company constructed a rivetless ship for the Texas Oil company using 11,000 pounds of welding wire. Rivets for that ship would have weighed 18,000 pounds.
- First Historical Zoning Ordinance – Oct 13, 1931
The Charleston City Council passed a Historic Preservation ordinance.
- First US senator elected by write-in vote – November 2, 1954
Strom Thurmond received 139,106 write-in votes to win a seat in the US Senate. He defeated Democratic nominee Edgar Brown, who received only 80,956 votes.