It connects Charterhouse Square and Holborn Circus, crossing Farringdon Road and running along a number of historical sites, including Smithfield Market and the historical headquarters of the Port of London Authority.

Before 1869, the one connection between the Smithfield area and the Charterhouse was an ancient street called Charterhouse Lane. In the seventeenth century this street consisted of a narrow alley which started from the east side of the open space at the bottom of St John Street, then widened a little and swung northwards on a straight line to the gate that protected Charterhouse Yard. The opening-out of the western section when the new Smithfield Market was built in the 1860s destroyed the old lane’s integrity. Less than half its former length remained, renamed as part of the otherwise entirely new Charterhouse Street

Charterhouse Street is perhaps most famous for its gastropubs, such as the Fox and Anchor, that attract local City workers and is a popular venue for revellers, with Fabric nightclub located at No. 77A. The street was the home of several cold stores serving Smithfield Meat Market including the Central Cold Store and the Metropolitan Cold Stores at 77A.

The site on the corner of Farringdon Road was occupied by the 1960s Caxton House which was demolished in 2009 as part of the Farringdon station extension.

The nearest London Underground stations are Barbican at the east end of Charterhouse Street and Farringdon at the west end. Farringdon station also provides a connection to the Crossrail and Thameslink rail services.