It is thought to take its name from a Greek church that was built in 1677 in adjacent Crown Street, now part of the west side of Charing Cross Road. The church is depicted in William Hogarth's 'Noon' from Four Times of the Day.
Although the street has several houses from the 18th century and earlier, it is mainly 19th-century in appearance.
No. 1 Greek Street is the House of St Barnabas, built in 1746. It became the offices of the Westminster Commissioner for Works for Sewers in 1811. This is where Chief Engineer Sir Joseph Bazalgette started to work on the construction of the London sewerage system. By 1862 the house had been taken over by The House of Charity, which was established in 1846 to provide temporary accommodation for homeless people. Charles Dickens used the house and gardens as a model for the London lodgings of Dr Manette and Lucy in A Tale of Two Cities.
There has been a public house known as Pillars of Hercules at no. 7 since 1733. The current pub building sports some artwork by Invader and was long favoured by many figures in the London literary scene, including Martin Amis, Ian Hamilton, Julian Barnes and Ian McEwan. Indeed, Clive James named his second book of literary criticism (At the Pillars of Hercules) after it.