The junction has been a very busy traffic interchange since construction, as it lies at the centre of Theatreland and handles exit traffic from Piccadilly, which Charles Dickens, Jr. described in 1879: "Piccadilly, the great thoroughfare leading from the Haymarket and Regent-street westward to Hyde Park-corner, is the nearest approach to the Parisian boulevard of which London can boast." The circus lost its circular form in 1886 with the construction of Shaftesbury Avenue.

Piccadilly Circus tube station was opened 10 March 1906, on the Bakerloo Line, and on the Piccadilly Line in December of that year. In 1928, the station was extensively rebuilt to handle an increase in traffic.

The intersection’s first electric advertisements appeared in 1910, and, from 1923, electric billboards were set up on the facade of the London Pavilion. Traffic lights were first installed on 3 August 1926, at the junction.

The Shaftesbury Memorial Fountain in Piccadilly Circus was erected in 1893 to commemorate the philanthropic works of Anthony Ashley Cooper, 7th Earl of Shaftesbury. During the Second World War, the statue atop the Shaftesbury Memorial Fountain was removed and was replaced by advertising hoardings. It was returned in 1948. When the Circus underwent reconstruction work in the late 1980s, the entire fountain was moved from the centre of the junction at the beginning of Shaftesbury Avenue to its present position at the southwestern corner.