Cheapside links St. Martin’s Le Grand with Poultry. Near its eastern end at Bank junction, where it becomes Poultry, is Mansion House, the Bank of England, and Bank station. To the west is St. Paul’s Cathedral, St. Paul’s tube station and Paternoster Square.

In the Middle Ages, it was known as Westcheap, as opposed to Eastcheap, another street in the City, near London Bridge. The boundaries of the wards of Cheap, Cordwainer and Bread Street run along Cheapside and Poultry; prior to boundary changes in 2003 the road was divided amongst Farringdon Within and Cripplegate wards in addition to the current three.

Cheapside is a common English street name, meaning "market place". There was originally no connection to the modern meaning of cheap (’low price’, a shortening of good ceap, ’good buy’), though by the 18th century this association may have begun to be inferred.

Many of the streets feeding into the main thoroughfare are named after the produce that was once sold in those areas of the market, including Honey Lane, Milk Street, Bread Street and Poultry.

In medieval times, the royal processional route from the Tower of London to the Palace of Westminster would include Cheapside. During state occasions such as the first entry of Margaret of France (second wife of King Edward I), into London in September 1299, the conduits of Cheapside customarily flowed with wine.

During the reign of Edward III in the 14th century, tournaments were held in adjacent fields. The dangers were, however, not limited to the participants: a wooden stand built to accommodate Queen Philippa and her companions collapsed during a tournament to celebrate the birth of the Black Prince in 1330. No one died, but the King was greatly displeased, and the stand’s builders would have been put to death but for the Queen’s intercession.

On the day preceding her coronation, in January 1559, Elizabeth I passed through a number of London streets in a pre-coronation procession and was entertained by a number of pageants, including one in Cheapside.

Meat was brought in to Cheapside from Smithfield market, just outside Newgate. After the great Church of St. Michael-le-Querne, the top end of the street broadened into a dual carriageway known as the Shambles (referring to an open-air slaughterhouse and meat market), with butcher shops on both sides and a dividing central area also containing butchers. Further down, on the right, was Goldsmiths Row, an area of commodity dealers. From the 14th century to the Great Fire, the eastern end of Cheapside was the location of the Great Conduit.

Cheapside was the birthplace of John Milton, and Robert Herrick. It was for a long time one of the most important streets in London. It is also the site of the ’Bow Bells’, the church of St. Mary-le-Bow, which has played a part in London’s Cockney heritage and the tale of Dick Whittington. Geoffrey Chaucer grew up around Cheapside and there are a scattering of references to the thoroughfare and its environs throughout his work. The first chapter of Peter Ackroyd’s Brief Lives series on Chaucer also colourfully describes the street at that time. Thomas Middleton’s play A Chaste Maid in Cheapside (1613) both satirises and celebrates the citizens of the neighbourhood during the Renaissance, when the street hosted the city’s goldsmiths.

Cheapside was extensively damaged during The Blitz in late 1940 and particularly during the Second Great Fire of London. Much of the rebuilding following these raids occurred during the 1950s and 1960s and included a number of unsympathetic contemporary attempts at recreating the centuries-old architecture that had been destroyed. In recent years many of these buildings have themselves been demolished as a programme of regeneration takes place along Cheapside from Paternoster Square to Poultry.

Cheapside today is a street of offices and developments of retail outlets. It can no longer be described as "the busiest thoroughfare in the world" (as in Charles Dickens’ day) and is instead simply one of many routes connecting the East End and the City of London with the West End.