The area around Glasgow has hosted communities for millennia, with the River Clyde providing a natural location for fishing. The Romans later built outposts in the area and, to protect Roman Britannia from the Brittonic speaking (Celtic) Caledonians, constructed the Antonine Wall. Items from the wall, such as altars from Roman forts like Balmuildy, can be found at the Hunterian Museum today.

Glasgow itself was reputed to have been founded by the Christian missionary Saint Mungo in the 6th century. He established a church on the Molendinar Burn, where the present Glasgow Cathedral stands, and in the following years Glasgow became a religious centre. Glasgow grew over the following centuries. The Glasgow Fair reportedly began in 1190. The first bridge over the River Clyde at Glasgow was recorded from around 1285, giving its name to the Briggait area of the city, forming the main north–south route over the river via Glasgow Cross. The founding of the University of Glasgow in 1451 and elevation of the bishopric to become the Archdiocese of Glasgow in 1492 increased the town's religious and educational status and landed wealth. Its early trade was in agriculture, brewing and fishing, with cured salmon and herring being exported to Europe and the Mediterranean.

Following the European Protestant Reformation and with the encouragement of the Convention of Royal Burghs, the 14 incorporated trade crafts federated as the Trades House in 1605 to match the power and influence in the town council of the earlier Merchants' Guilds who established their Merchants House in the same year.Glasgow was subsequently raised to the status of Royal Burgh in 1611. Glasgow's substantial fortunes came from international trade, manufacturing and invention, starting in the 17th century with sugar, followed by tobacco, and then cotton and linen, products of the Atlantic triangular slave trade.

Daniel Defoe visited the city in the early 18th century and famously opined in his book A tour thro' the whole island of Great Britain, that Glasgow was "the cleanest and beautifullest, and best built city in Britain, London excepted". At that time the city's population was about 12,000, and the city was yet to undergo the massive expansionary changes to its economy and urban fabric, brought about by the Scottish Enlightenment and Industrial Revolution.