The station was opened by the Central London Railway (CLR) on 30 July 1900 with the name Post Office, after the headquarters of the General Post Office on St Martin's Le Grand. The name Post Office was possibly chosen instead of the more obvious St Paul's to differentiate it from a South Eastern Railway (SER) station of that name (which today is called Blackfriars).
The station entrance was originally located on the north side of Newgate Street, on the west side of the junction with King Edward Street, but was moved to the east when the station was modernised in the 1930s with an underground ticket hall and escalators. A modern ventilation shaft in the centre of the traffic island at the junction indicates the location of the original lift shafts. When the SER station called St Paul's was renamed Blackfriars in 1937, the Underground station called Post Office took the name St Paul's, which it has kept ever since.
At the end of the 19th century, Newgate Street was a narrow road with some of its mediaeval character remaining. To reduce land purchase and compensation payments, the CLR routed its tunnels directly under public roads. At St Paul's the narrowness of the road required the tunnels to be placed one above the other with the westbound tunnel uppermost. The lifts originally operated to a level between the two platforms, with stairs up or down to the platforms as necessary. A high-level access passage way is visible at the lowest level leading to the disused lift lobby.
During the Second World War the electricity grid control room for London and Southeast England was housed below ground in the lift shaft.