Santander is to close 140 branches, putting 1,270 jobs at risk, the bank announced on Wednesday.
The company is in talks with unions to try to find new roles for staff affected where possible and said it expects a third to be redeployed.
Customers will be supported in finding alternative branches among the 614 that will remain open, Santander said.
The bank blamed a 23 per cent fall in the number of transactions in branches over the last three years, during which time digital transactions have almost doubled.
UK banks have closed 3,101 branches since 2015, according to figures from Which?
RBS, which owns NatWest, and Ulster Bank shut 476 branches over the course of last year and this month, while Lloyds Banking Group closed 131.
The number of cash machines has also dropped, particularly in rural areas, raising concerns that many consumers are being denied access to financial services.
Santander’s branch closures will come as a blow for those who rely on traditional banking services, said Gareth Shaw, head of Which? Money.
“While online banking is on the rise, a third of the country still does not use it and, as we’ve seen from a recent spate of IT failures, such systems are not infallible,” he said.
“Despite the switch to digital ways of banking and paying, millions of consumers still need access to cash.”
Susan Allen, head of retail and business banking, said the way customers use their bank has changed “dramatically” in recent years.
“As a result, we have had to take some very difficult decisions over our less visited branches, and those where we have other branches in close proximity,” Ms Allen said.
Branches still have a “vital role to play”, she added.
Santander’s announcement came as cash machine network operator Link unveiled plans aimed at saving cash machines in remote locations.
Credit and debit card operators will pay a “super supplement” to cash machine operators for transactions on some ATMs.
The fee will rise to a maximum of £2.75, a move which Link hopes will ensure the viability of free-to-use cash machines in rural areas.
In November, the House of Commons Treasury Committee launched a probe into the effect of bank branch closures amid fears that vulnerable people were being hit hardest.
MPs will scrutinise whether certain groups of people are excluded from obtaining a basic level of service and whether vulnerable consumers pay more for financial services products.