Prior to European contact in the 17th century, the present site of London was occupied by numerous Algonquin and Iroquois villages; the Algonquin village at the forks of Askunessippi (now called the Thames River) was called Kotequogong.

This location was selected to be the site of the future capital of Upper Canada in 1793 by
Lieutenant-Governor John Graves Simcoe. It was Simcoe who named the settlement after London, England and also renamed the river; however, his choice was initially rejected by Guy Carleton, (Governor Dorchester), who made the comment that "access to London would be limited to hot-air balloons".

The village itself was not founded until 1826 and never became the capital envisioned by Simcoe. It was part of the Talbot Settlement, overseen by Colonel Thomas Talbot, who oversaw the surveying of the land and built the first government buildings for the administration of the Western Ontario region.

With the rest of Southwestern Ontario which was part of this settlement, it benefited from Talbot's provisions for building and maintaining roads and for assignment of priority for access to main roads to productive land (rather than to Crown and clergy reserves, which received preference in the rest of Ontario).

London’s early history was not without challenges.

• In 1832 the new settlement suffered an outbreak of cholera.
• On April 13, 1845, a large fire destroyed much of the town, which was at the time filled with mostly wooden buildings.
• One of the first casualties of the fire was the town's only fire engine.
• On May 24, 1881, the ferry SS Victoria capsized in the Thames River, drowning approximately 200 passengers, the worst disaster in London's history.
• Two years later, on July 12, 1883, the first of the two most devastating floods in London's history killed 17 people.
• The second major flood occurred on April 26, 1937, which destroyed more than 1000 homes and caused millions of dollars in damages, particularly in West London.
• After repeated floods the Upper Thames River Conservation Authority built Fanshawe Dam to control the level of the Thames; it opened in 1952. Financing came from the federal, provincial, and municipal governments.

London became a vacation spa for the wealthy, when in the 1860s, sulphur hot springs were discovered at the forks of the Thames River while industrialists were drilling for oil. The springs became a popular destination for wealthy Ontarians, until the turn of the 20th century when a textile factory was built at the site, replacing the spa.

In 1875, London's first iron bridge, the Blackfriars Street Bridge, was constructed. A rare example of a bowstring through truss bridge, it remains open to traffic today. The bridge was produced by the Wrought Iron Bridge Company of Canton, Ohio; however, a local contractor, Isaac Crouse (1825-1915), was the contractor who undertook the actual erection of the bridge.

Although many repairs and modifications have been made to the Blackfriars Bridge, the structure remains an historic relic designated under Part IV of the Ontario Heritage Act, still serving its original purpose.

London's role as a military center continued into the 20th Century during the two World Wars, serving as the administrative centre for the Western Ontario district. Today there is still an active Garrison Support Unit in the city at Wolseley Barracks.

The City of London is currently the 13th largest city in Canada and the 5th largest city in Ontario.