The character of Spitalfields that shaped its built environment most profoundly came from the Huguenots — French Protestant refugees who fled to England after Louis XIV revoked the Edict of Nantes in 1685, destroying their legal protections. In December 1687, a committee established to help the refugees reported that 13,050 French refugees had settled in London, primarily around Spitalfields.

They chose the area deliberately: it lay just outside the City of London's boundaries, which meant they could practice their trade without being bound by the City guilds' restrictive regulations. Their trade was silk weaving, and they transformed Spitalfields. The grand terraced houses they built for master weavers still line streets like Fournier Street and Elder Street. Nicholas Hawksmoor's Christ Church Spitalfields, built during the reign of Queen Anne, was intended partly to demonstrate the power of the established church to the largely dissenting Huguenot community. It looms over the neighborhood still.

By the Victorian era, the Huguenot silk industry had collapsed — a trade treaty with France in 1860 opened the market to cheaper French imports, leaving weavers unemployed across Spitalfields, Bethnal Green, and Shoreditch. The large-windowed weavers' houses proved well suited to tailoring, attracting a new wave of arrivals: Jewish refugees from Eastern Europe, fleeing pogroms and poverty. The area became known as "Little Jerusalem" in the 19th century.

By the 1880s, inner Spitalfields had also become notorious for poverty and crime. Flower and Dean Street was described in 1881 as "perhaps the foulest and most dangerous street in the metropolis." Dorset Street, nearby, earned its own grim fame in the autumn of 1888, when Mary Jane Kelly was murdered there — the final victim attributed to Jack the Ripper. The women who lived and died in Spitalfields during the Whitechapel Murders of 1888 were working-class women living in poverty in common lodging houses. They were mothers, wives, people with histories. Spitalfields has not forgotten them.

In the late 20th century, the Jewish community diminished and Bangladeshi immigrants arrived, working in the same textile trades and establishing what became known as the curry capital of London — Brick Lane lined with restaurants, its northern stretch hosting the weekly Brick Lane Market. By 1981, at least 60% of Spitalfields households were of minority ethnic origin.

From the 1960s onward, a parallel movement worked to save the old Huguenot merchant houses from demolition. The Spitalfields Historic Buildings Trust preserved many of them — an effort that succeeded in protecting the architecture but also contributed to significant gentrification. Property prices climbed. Artists, writers, and architects moved in alongside the communities already there. Gilbert & George live on Fournier Street. Jeanette Winterson runs a delicatessen on Brushfield Street. The area holds its tensions between preservation and affordability, between memory and development.

A remarkable detail about Fournier Street is that its most prominent building has been, in succession, a Huguenot chapel, a Methodist chapel, a Jewish synagogue, and now a mosque — the same structure serving successive waves of immigrant communities over three centuries. This continuity within change is Spitalfields in miniature.

The Spitalfields Mathematical Society, established here in 1717 by working weavers who gathered to discuss mathematics, merged with the Royal Astronomical Society in 1846. Samuel Gompers, founder of the American Federation of Labor, was born in Spitalfields in 1850 into a Jewish family of cigarmakers before emigrating to New York. Mary Wollstonecraft, the early feminist writer, was born here in 1759. The area has produced radicals, artists, activists, and scientists across its long history of receiving people who had nowhere else to go and finding ways to make something from that condition.