TSB said it will close 70 branches in 2022 because fewer people are using them, leaving them with 220.
Union Unite said TSB's cuts would be a "bitter blow" for the communities affected and called on the government to protect people's access to cash and other services.
TSB, which is owned by Spain's Sabadell, said it would still have Britain's seventh largest branch network following the cuts and none of the closures were the "last branch in town".
Ten new 'pop-up' branches will be opened, the bank said.
The bank said the cuts would result in 150 fewer roles, but affected staff would be offered alternative jobs.
"We expect the vast majority of colleagues to be redeployed into other roles in TSB," a spokesperson for the bank said.
"Closing branches is an incredibly difficult decision to take, but we have to respond to the changes in the way people bank," TSB Chief Customer Officer Robin Bulloch said.
British banks have stepped up branch closures in recent months, with Lloyds cutting 48 and Virgin Money saying it would close almost one in five branches.
Sabadell has said it has no plans for now to sell TSB after recently rejecting an unsolicited offer from Co-op Bank. Sabadell had frozen previous plans to sell TSB until it completely turns around the business.
As part of Sabadell's overall three-year strategy it targeted improved returns at TSB by increasing mortgages and cutting costs.
(Reporting by Iain Withers, additional reporting by Jesus Aguado in Madrid, editing by Kirstin Ridley and Jason Neely)
By Iain Withers
