As London spread beyond its northern wall in the 16th and 17th centuries, Clerkenwell and its environs became residential. In Islington and in Clerkenwell, medicinal wells were discovered, and one famous spa gave its name to the Sadler's Wells Theatre built on its site. Gradually, however, the rural pleasure gardens were overtaken by urban growth associated with the Regent's Canal (started 1812), the New North Road (1812) and other roads, and the North London Railway (1850s). Canonbury Square, Lloyd Square, and Myddleton Square were created in the late 18th and early 19th centuries.

Many famous religious dissenters, including John Bunyan (Bunyan, John), Daniel Defoe (Defoe, Daniel), Isaac Watts (Watts, Isaac), William Blake (Blake, William), and George Fox (Fox, George), the founder of the Society of Friends (Quakers), are buried at Bunhill Fields, City Road. Facing the cemetery is Wesley's Chapel, with the house (now a museum) and burial place of John Wesley (Wesley, John). Also associated with the borough are John Milton (Milton, John), who lived on Bunhill Row; Samuel Johnson (Johnson, Samuel), who worked at St. John's Gate; Oliver Goldsmith (Goldsmith, Oliver), who occupied Canonbury House; Edward Lear (Lear, Edward), who lived in Bowman's Mews; caricaturist George Cruikshank (Cruikshank, George), who lived in Amwell Street; and Charles Lamb (Lamb, Charles), who lived on Duncan Terrace. Film director Alfred Hitchcock (Hitchcock, Sir Alfred) got his start at Islington Studios.

Notable theatres are the Tower Theatre at the 16th-century Canonbury Tower; the Little Angel Theatre, which features marionettes; and Sadler's Wells, which opened in 1683 (the present theatre, built in 1931, is famous for opera and ballet performances). Buildings of historic interest include the 14th-century Charterhouse, which was built as a Carthusian monastery and later became a hospital and school. The Armoury House of the Honourable Artillery Company was constructed in the 1730s on Artillery Ground, which has been in use since 1642. Educational institutions include the City University (founded 1894 as Northampton Institute; university status 1966) and the University of North London (founded 1971 as Polytechnic of North London; university status 1992).

The service sector dominates the economy, but there is some light manufacturing, and traditional craft shops survive in the Clerkenwell district. The London-Edinburgh railway approaches King's Cross Station through the borough, which is well served by London Underground (subway) lines.