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The first known written mention of the Isle of Dogs is in the 'Letters & Papers of Henry VIII'. In Volume 3: 1519-1523. 2 October 1520. No. 1009 - 'Shipping', there is a list of purchases, which includes "A hose for the Mary George, in dock at the Isle of Dogs, 10d".

Brewer's 1898 Dictionary of Phrase and Fable attributes the name: "So called from being the receptacle of the greyhounds of Edward III. Some say it is a corruption of the Isle of Ducks, and that it is so called in ancient records from the number of wild fowl inhabiting the marshes." Other sources discount this, believing these stories to all derive from the antiquarian John Strype, and believe it might come from one of the following:

• a nickname of contempt: Ben Jonson and Thomas Nashe wrote a satirical play in 1597, which was a mocking attack on the island of Great Britain, titled The Isle of Dogs, which offended some in the nobility. Jonson was imprisoned for a year; Nashe avoided arrest by fleeing the area. Samuel Pepys referred to the "unlucky Isle of Dogs."
• the presence of Dutch engineers reclaiming the land from a disastrous flood.
• the presence of gibbets on the foreshore facing Greenwich.
• a yeoman farmer called Brache, this being an old word for a type of hunting dog.
• the original docks located here were used for firewood importation and the phrase is linked to "fire dogs", the cross-beams beneath a hearth fire, hence Isle of Dogs.
• the dogs of a later king, Henry VIII, who also kept deer in Greenwich Park. Again it is thought that his hunting dogs might have been kept in derelict farm buildings on the Island.
• Isle of Dykes, which then got corrupted over the years.

The whole area was once simply known as Stepney Marsh; Van den Wyngaede's "Panorama of London" dated 1543 depicts and refers to the Isle of Dogs. Records show that ships preparing to carry the English royal household to Calais in 1520 docked at the southern bank of the Island. The name Isle of Dogges occurs in the Thamesis Descriptio of 1588, applied to a small island in the south-western part of the peninsula. The name is next applied to the Isle of Dogs Fam (originally known as Pomfret Manor) shown on a map of 1683. At the same time, the area was variously known as Isle of Dogs or the Blackwell levels. By 1855, it was incorporated within the parish of Poplar under the aegis of the Poplar Board of Works. This was incorporated into the Metropolitan Borough of Poplar on its formation in 1900.

After the building of the Docks (especially the West India Docks and the adjacent City Canal), and with an increasing population, locals increasingly referred to the area as The Island. This area includes Millwall, Cubitt Town, and Blackwall. The south of the isle opposite Greenwich was once known as North Greenwich, now applied to the area around the Millennium Dome on the Greenwich Peninsula. Between 1986 and 1992 it enjoyed a brief formal existence, as the name Isle of Dogs was applied to one of seven neighbourhoods to which power was devolved from the council. The neighbourhood was later abolished.

It was the site of the highest concentration of council housing in England but is now best known as the location of the prestigious Canary Wharf office complex. One Canada Square, also known as the Canary Wharf Tower, is the second tallest habitable building in Britain at 244 metres (801 ft). The peninsula is an area of social extremes, comprising some of the most prosperous and most deprived areas of the country; in 2004, nearby Blackwall was the 81st most deprived ward in England out of over 8,000, while the presence of Canary Wharf gives the area one of the highest average incomes in the UK.