The NatWest bank is to open a new branch at Bankside Mix in Southwark Street.
The new branch, which is due to open in April, is on the ground floor of one of the two Bankside office blocks occupied by NatWest's parent company RBS Group.
NatWest originally proposed to open the bank in 2009 but plans were put on hold.
The new NatWest branch will open just weeks before HSBC shuts its nearby Blackfriars branch.
For the latest local news and events direct to your inbox every Monday, you need our weekly email newsletter SE1 Direct.