The Meadville area was the ancestral land of the Eriechronon people until the Iroquois Confederacy forced them out. Having been displaced from their ancestral lands in what is now Eastern Pennsylvania, the Lenape moved into the now unoccupied region.
They formed an alliance with the neighboring Seneca, one of the five tribes that made up the Iroquois Confederacy, and other displaced Lenape. Under the leadership of Chief Custaloga, they founded the settlement of Cussewago. Custaloga's name first appeared
in western Pennsylvania's history in George Washington's journal of 1754. When Washington arrived in the village of Venango (Fort Machault), Custaloga was in charge of the wampum of his nation. This wampum was a message that was sent to the Six Nations if the
French refused to leave the land. Custaloga was the chief of the Munsee or Wolf Clan of Delawares and he also ruled over the Delawares at the town of Cussewago, at the present site of Meadville.

After Cussewago was abandoned, Meadville was laid out by William McArthur Sr. and settled on May 12, 1788, by a party of settlers led by David Mead. Its location at the confluence of Cussewago Creek and French Creek was only a day's travel by boat to the safety
of Fort Franklin. The neighboring Iroquois and Lenape befriended the isolated settlement, but their enemies, including the Wyandots, were not so amiable. The threat of their attacks caused the settlement to be evacuated for a time in 1791. Around 1800, many of the
settlers to the Meadville area came after receiving land bounties for service in the American Revolutionary War. Allegheny College was founded in April 1815 by Timothy Alden. Meadville became an important transportation center after the construction of the French
Creek Feeder Canal in 1837 and of the Beaver and Erie Canal it connected to at Conneaut Lake and subsequent railroad development.

In the late 18th and early 19th centuries, Meadville played a small part in the Underground Railroad helping escaping slaves to freedom. An event in September 1880 led to the end of segregation by race in the state's public schools. At the South Ward schools,
Elias Allen tried unsuccessfully to enroll his two children. He appealed to the Crawford County Court of Common Pleas, and Judge Pearson Church declared unconstitutional the 1854 state law mandating separate schools for Negro children. This law was amended,
effective July 4, 1881, to prohibit such segregation.

By the late 19th century, Meadville's economy was also driven by logging, agriculture, and iron production. The Talon Corporation, headquartered in Meadville, played a major role in the development of the zipper. Since the clothing industry was largely unaffected
by the Great Depression, the community saw a population boom at that time. During World War II, the nearby Keystone Ordnance plant brought additional jobs to the area.

The high demand for zippers created favorable conditions for the Talon Company, and so became Meadville's most crucial industry. The company encountered significant difficulties after it was absorbed by Textron industries in 1968, eventually ending up bankrupt.
However, as a result of the need for close tolerances and tool and die makers, a cottage industry of tool and die shops was established which resulted in Meadville, earning the city the nickname Tool City with more tool shops per capita than any place else in the United States.

In 1886, a blacksmith from Evansburg, Pennsylvania, George B. DeArment, began hand-forging farrier's tools and selling them from town to town out of the back of a wagon. The business eventually became known as the Champion Bolt and Clipper Company. In 1904, now named
Channellock, the company moved to a 12,000-square-foot (1,100 m2) facility in Meadville and added nippers, pinchers, and open-end wrenches to its product line. George B. DeArment's two sons, Almon W. and J. Howard DeArment became partners in the company in 1911 and expanded
the product line again to include hammers. In 1923, the company moved again to a 33,000-square-foot (3,100 m2) facility at its current location. Four years later, the name of the company was changed to the Champion–DeArment Tool Company.

Talon remained a major employer, along with the Erie Railroad, American Viscose Corporation (later known as Avtex Fibers), Channellock tools, and Dad's Pet Food. The area actually saw an increase in population during the Great Depression and the economy continued to
grow past World War II. By the early 1990s, Channellock and Dad's were the only large companies operating in Meadville. This blow to the local economy was softened by a subsequent surge in light industry, mainly tool and die machine shops. The song "Bittersweet Motel" by
Vermont jam band, Phish, was inspired when keyboardist Page McConnell left a wedding in Meadville and drove to the Pittsburgh Airport.

The population was 13,050 at the 2020 census.

A Concise History of the City of Meadville By Anne W. Stewart