Santander said it would close 140 branches, affecting 1,270 staff, of which about one third would be offered alternative roles in the company.
It meanwhile plans to retain 614 branches across the UK.
“The way our customers are choosing to bank with us has changed dramatically in recent years, with more and more customers using online and mobile channels,” said Susan Allen, head of retail and business banking at Santander.
“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,” she added in Wednesday's statement.
Santander said that the number of transactions carried out via Santander branches had dropped by almost one quarter in the last three years.
Transactions via digital channels had doubled over the same period.
“We continue to believe that branches have a vital role to play and we will be refurbishing 100 of our branches over the next two years,” Allen added.