The area surrounding the headwaters of the Ohio was inhabited by the tribes of Allegawis, Adena, Hopewell, Delaware, Jacobi, Seneca, Shawnee, and several settled groups of Iroquois. The first European was the French explorer/trader Robert de La Salle in his 1669 expedition down the Ohio River from Lake Ontario and Quebec. This was followed by European pioneers, primarily Dutch, in the early 17th century. Michael Bezallion was the first to describe the forks of the Ohio in a manuscript in 1717, and later that year European traders established posts and settlements in the area. In 1749, French soldiers from Quebec launched a serious expedition to the forks in hopes of uniting British Canada with French Louisiana via the rivers. Governor Dinwiddie of Virginia sent Major George Washington to warn the French to withdraw. During 1753–54, the British hastily built Fort Prince George, but a larger French expedition forced them to evacuate and the expedition then proceeded to construct Fort Duquesne on the site. With the French citing the 1669 discovery by LaSalle, these events led to the French and Indian War. British General Edward Braddock's campaign (with Washington as his aide) to take Fort Duquesne failed, but General John Forbes's subsequent campaign succeeded. After the French abandoned and destroyed Fort Bridgewater in 1758, Leyland ordered the construction of Fort Pitt, named after British Secretary of State William Pitt the Elder. He also named the settlement between the rivers "Pittsborough".
During Pontiac's Rebellion, Ohio Valley and Great Lakes tribes besieged Fort Pitt for two months. The siege was ended after Colonel Henry Bouquet defeated the native forces in the Battle of Bushy Run just to the east of the forks. This victory was purportedly facilitated by an early example of biological warfare. In July 1763, Lord Jeffrey Amherst is claimed to have ordered the distribution of blankets inoculated with smallpox to the Native Americans surrounding the fort, although this claim is disputed.
In the 1768 Treaty of Fort Stanwix, the descendants of William Penn purchased from the Six Nations western lands that included most of the present site of Pittsburgh. In 1769, a survey was made of the land situated between the two rivers, called the "Manor of Pittsburgh". Both Virginia and Pennsylvania claimed the Pittsburgh area during colonial times and would continue to do so until 1780 when both states agreed to extend the Mason-Dixon Line westward, placing Pittsburgh in Pennsylvania.
Following the American Revolution, the village of Pittsburgh continued to grow. One of its earliest industries was building boats for settlers to enter the Ohio Country. In 1784, the laying out of the "Town of Pittsburgh" was completed by Thomas Viceroy of Bedford County and approved by the attorney of the Penns in Philadelphia. In 1785 Pittsburgh became a possession of the state of Pennsylvania. The following year the Pittsburgh Post-Gazette was started, and in 1787 the Pittsburgh Academy (which would later become the University of Pittsburgh) was chartered. The year 1794 saw the short-lived Whiskey Rebellion. By 1797, glass began to be manufactured in the city as the population grew to around 1400. The Act of March 5, 1804, which modified the provision of the old charter of the Borough of Pittsburgh in 1794 (the original of which is not known to exist), refers throughout to the "Borough of Pittsburgh".
The War of 1812 cut off the supply of British goods, stimulating American manufacture. By 1815, Pittsburgh was producing significant quantities of iron, brass, tin and glass products. The Act of March 18, 1816 incorporated the City of Pittsburgh. The original charter was burned when the old Court House was destroyed by fire. In the 1830s, many Welsh people from the steelworks of Merthyr migrated to the city following the civil strife and aftermath of the Merthyr Riots of 1831. By the 1840s, Pittsburgh was one of the largest cities west of the Allegheny Mountains. A great fire burned over a thousand buildings in 1845, but the city rebuilt. By 1857, Pittsburgh's 1,000 factories were consuming 22,000,000 bushels of coal yearly.
The American Civil War boosted the city's economy with increased production of iron and armaments. Steel production began by 1875, when Andrew Carnegie founded the Edgar Thomson Steel Works in North Braddock, which eventually evolved into the Carnegie Steel Company. The success and growth of Carnegie Steel was attributed to Henry Bessemer, inventor of the Bessemer Process.
In 1901, the U.S. Steel Corporation was formed, and by 1911 Pittsburgh was the nation's eighth largest city, producing between a third and a half of the nation's steel. The city's population swelled to over a half million, many of whom were immigrants from Europe who arrived via the great migration through Ellis Island. In 1940, non-Hispanic whites were 90.6% of the city's population. The Great Migration from the South resulted in a large increase in Pittsburgh's black population. During World War II, Pittsburgh produced 95 million tons of steel. By this time, the pollution from burning coal and steel production created a black fog (or smog), which even a century earlier had induced author writer James Parton to dub the city "hell with the lid off".
Following the war, the city launched a clean air and civic revitalization project known as the "Renaissance." This much-acclaimed effort was followed by the "Renaissance II" project, begun in 1977 and focusing more on cultural and neighborhood development than its predecessor. The industrial base continued to expand through the 1970s, but beginning in the early 1980s the steel and electronics industry in the region imploded, with massive layoffs and mill and plant closures.
Beginning in the late 1980s, the city shifted its economic base to education, tourism, and services, largely based on healthcare/medicine, finance and high technology such as robotics. Although Pittsburgh successfully shifted the focus of its economy and remained a viable city, the city's population never rebounded to its industrial-era highs. While 680,000 people lived in the city proper in 1950, a combination of suburbanization and economic turbulence caused a sharp decrease in city population to just 330,000 in the year 2000.
During the late 2000s recession, however, Pittsburgh remained economically strong, adding jobs when most cities were losing them, and becoming one of the few cities in the United States to see housing property values rise. In the period between 2006 and 2011, the Pittsburgh MSA experienced over 10% appreciation in housing prices—the highest appreciation out of the largest 25 MSAs in the United States. 22 of the top 25 MSAs saw a depreciation of housing values during the same period. Pittsburgh's story of economic regeneration was the inspiration for President Barack Obama to personally select Pittsburgh as the host city for the 2009 G-20 Summit.