Lisson Green is described as a hamlet in the Domesday Book in 1086, the edges of the settlement defined by the two current Edgware Road stations facing onto Edgware Road or Watling Street as it was previously known, one of the main Roman thoroughfares in and out of London. Occasionally referred to as Lissom Grove, originally Lisson Grove was part of the medieval manor of Lilestone which stretched as far as Hampstead. Lisson Green as a manor broke away c. 1236 with its own manor house. Paddington Green formed part of the original Lilestone estate.

Attractions One of Lisson Green village's first attractions would have been the Yorkshire Stingo, a public house probably visited by Samuel Pepys in 1666 on a visit with a flirtatious widow. Stingo was the name of a particular Yorkshire ale. On Saturdays during the 1780s, lascars, former sailors from Bengal, Yemen, Portuguese Goa employed by the East India Company left stranded and destitute in London would gather to receive a small subsidy.

18th century Until the late 18th century the district remained essentially rural. The Austrian composer Joseph Haydn moved briefly to a farm in Lisson Grove in the spring of 1791 in order to have quiet surroundings in which to compose during his three-year stay in England. The historical painter Benjamin Haydon described a Lisson Grove dinner party with William Wordsworth, John Keats and Charles Lamb at which Lamb got drunk and berated the ‘rascally Lake poet' for calling Voltaire a dull fellow. In 1792 The Philological School was opened on the corner of Lisson Grove and Marylebone Road.

19th century Nowadays Lisson Grove is a much improved section of West London, but for over a hundred years it was one of the capital's worst slums. The area was notorious for drinking, crime and prostitution, as well as the extreme poverty of the people and the squalor and dilapidation of the homes they lived in. Local police officers only patrolled the district in pairs, and they described the women of the area as the most drunken, violent and foul-mouthed in all London.The Quiver, 1896–1897. The Grove being between Marylebone and Paddington railway stations, and on top of a busy midsection of Regent's Canal, the industrialisation of the area was swift during the 19th century transforming the area from a pastoral outpost on the north western edge of London into a crossroads for goods, cargo and passengers. In 1880 the most substantial building in the road, Portman Buildings, was erected.

Regent's Canal arrived in rural Lisson Grove in 1810 and with the construction of Eyre's Tunnel or Lisson Grove Tunnel under Aberdeen Place in 1816 and Marylebone railway station by H W Braddock for the Great Central Railway on the Portman Nursery site at the end of the century, the rural Lisson Grove was quickly engulfed by the expanding city during the 1800s.

The Regency Era (1811–1820): William Blake, the Shoreham Ancients and The Brazen Head public house It was during the early 1800s that painters from the Royal Academy, including a coterie of various student artists calling themselves the Shoreham Ancients inspired and congregating around William Blake, began to settle in and around Lisson Grove. In 1812, John Linnell, who was to become a major patron of Blake's work, visited his friend Charles Heathcote Tatham, an architect who had built himself a majestic house in the open fields of the area of Lisson Grove between Park Road and Lisson Grove (the road) to paint the view of the surrounding fields of his garden. No. 34 Alpha Cottages is memorialised in the name of a block of flats on Ashmill Street, opposite Ranston (formerly Charles) Street and Cosway Street.

One such friend and colleague of Blake was Richard Cosway whose studio on Stafford Street was renamed as Cosway Street. "Cosway was not only a famous and fashionable painter; he was also a mesmerist and magician who practised arcana related to alchemical and cabbalistic teaching. There are reports of erotic ceremonies, the imbibing of drugs or 'elixirs', and ritual nudity. Blake was no stranger to the symbols or beliefs of a man such as Cosway – the manuscript of the poem he was writing contains many drawings of bizarre sexual imagery, including women sporting giant phalli and children engaged in erotic practices with adults."

In 1829 the Catholic church of Our Lady was built. Designed by J.J. Scoles in the new Gothic style, it was one of the first Catholic churches following the Catholic Emancipation Act. Nearby on Harewood Avenue the Convent of the Sisters of Mercy was also established as part of the Catholic Mission in St. John's Wood, serving the large Irish community attracted by the railway, canal and construction work. The same year George Shillibeer operated the first London omnibus from the Yorkshire Stingo taking passengers to Bank.

Off the southern end of Lisson Grove was Bell Street where, in 1860, Roger Evans established London's first Victorian Turkish bath at his house. A contemporary critical social commentary reads:

Ragged London is about life in the poorest parts of the capital and Hollingshead was, of course, referring only to the first such bath in London. The first Victorian Turkish bath was actually built near Cork in Ireland in 1856, while the first in England opened in Manchester in 1857.

During the latter part of the 19th century a number of artisans and workers' flats and cottages sprang up from social housing initiatives spearheaded by Octavia Hill and the Peabody Trust. Across the road from The Green Man Inn, in 1884 Miles Building was built by the Improved Industrial Dwellings Association, facing Bell Street and Penfold Place.

The lost North Bank and South Bank Nash villas John Nash as a director of the Regent's Canal Company formed in 1812 began building detached villas set in gardens facing onto either side of the section of the canal running parallel to Lodge Road. Ultimately destroyed in 1900 in order to make way for St John's Wood electricity sub-station (North Bank) and Lisson Grove housing estate (South Bank) the enclave of distinctive white villas bisected by the picturesque banks of the canal attracted a literary and journalist set such as George Eliot, along with East India Dock Company employees with a working interest in being near the villas along Lodge Road.

"North and South Bank, have charming, if somewhat dilapidated streets of small villas standing in their own gardens, that ran down to the water and towpath either side of the canal. Incidentally these streets, owing to the eccentricities of some of the inhabitants, and the secrecy provided by the high walls of the gardens, had acquired a somewhat sinister reputation." In 1836 the North Bank was mentioned as being associated with scandal in a local history 'at this point the East India Dock Company whose employees were fairly thick on the ground in St John's Wood'.

While Nash was developing his villas in the north east of Lisson Grove, nearest Regent's Park, Sir Edward Baker (who gave his name to Baker Street) acquired the southern part of Lisson Green in 1821 and built large blocks of flats as an extension of Marylebone. From 1825 Sir Edwin Landseer moved to No 1, St John's Wood Road on the corner of Lisson Grove in a small cottage on the site of Punker's Barn. The journalist George Augustus Henry Sala born in 1828, recalls growing up in Lisson Grove during the 1830s "when the principle public buildings were pawnbrokers, and 'leaving shops', low public houses and beershops and cheap undertakers."

1885: The Eliza Armstrong Scandal

The fictional Eliza Doolittle was born and raised in Lisson Grove and had to pay "four and six a week for a room that wasn't fit for a pig to live in" before coming under the tutelage of Professor Henry Higgins. These characters from George Bernard Shaw's 1913 play Pygmalion are best known to modern audiences from the Lerner and Loewe 1956 musical and 1964 film adaptation of the play, entitled My Fair Lady. In 1885 the case of 13-year-old Eliza Armstrong, who was sold to a brothel keeper for £5, caused such an outcry that the law was changed and so was the name of the street where she lived (from Charles Street to Ranston Street), such was the dishonourable reputation it had gained.

The Fever Dens of Charles Street Lisson Grove was then an area of slum housing with single room tenements. According to the Medical Officer in 1881 "Charles Street contains 33 houses and has a population of 423 all told, that the rooms are let out in tenements, nearly every room being occupied by a family".

In 1881 an editorial in the Marylebone Mercury during an outbreak of typhus fever gives a description of the area.