Lille owes its name – once spelled L'Isle – to the fact that it was founded, back in the 11th century, on an island in the Deûle River. It grew into a market town that was a key link for north–south trade (unlike the Roman-established east–west route).

The 12th century saw Lille fought over by the Counts of Flanders and kings of France, and in 1363 Marguerite of Flanders' marriage to Philip the Bold made Flanders part of the duchy of Burgundy, with Lille becoming one of the capitals of the Burgundian state, significantly increasing trade. It came under Habsburg control following the marriage of Marie of Burgundy, daughter of Charles the Bold, to Maximilian of Austria in 1477, later becoming Spanish when Charles V of Spain became emperor. The Spanish king's appointment of his daughter Isabelle as ruler of Flanders heralded Lille's 'Golden Century', when the city expanded between 1605 and 1606, and again between 1618 and 1621.

In 1667, the city was captured by French forces led personally by Louis XIV, who promptly set about fortifying his prize, creating the Vauban-designed Citadelle. September 1792 saw 35,000 Austrians lay siege to Lille, but despite only being defended by a small garrison, the Lillois were victorious.

The 19th century was a time of industrialisation, and the city was the centre of France's textile industry. In the 1850s, the miserable living conditions of the city's 'labouring classes' were exposed by the writer Victor Hugo.

During the late 20th century, Lille suffered from post-industrial decline but bounced back thanks in part to the arrival of TGV trains (in 1993) and the Eurostar (in 1994); in 2004 it was a European City of Culture. Today, it is France's 10th-largest city by metropolitan area and fourth-largest conurbation, with 1.9 million inhabitants (including 700,000 across the Belgian border). Some 36% of the population is aged under 25, giving it a youthful energy.