The trend has been accelerated by the pandemic, although branch transactions fell by a third over the two years before the virus crisis and declined by a further 50% in 2020, said the banking giant.
Mobile and online transactions have been growing by 20% each year, with almost two thirds of transactions now digital.
Most of the branches being closed are less than three miles from another Santander branch, and the furthest is five miles.
The closures will leave a network of 452 branches, while Santander said it expects to find alternative roles for a significant number of staff affected by the announcement.
Adam Bishop, head of branches at Santander, said: “Branch usage by customers has fallen considerably over recent years so we have made the difficult decision to consolidate our presence in areas where we have multiple branches relatively close together.
“We will provide every support to customers of closing branches to find alternative ways to bank with us that best suit their individual needs.
“We are also working alongside our unions to support colleagues through these changes and to find alternative roles for those impacted wherever possible.
“We continue to believe that branches have an important role to play and we expect the size of our network to remain stable for the foreseeable future.”
The Communication Workers Union said it had reached a ground-breaking agreement with Santander on new ways of working which will preserve jobs and avoid compulsory redundancies that would otherwise have been “inevitable”.
National officer Sally Bridge said: “Recent membership surveys have indicated a desire from a large majority of those currently working from home for flexibility to continue after the pandemic, and this agreement achieves that for the majority of employees affected by these changes.
“Ultimately, however, faced with the proposals of site closures and consolidations, the deal we’ve negotiated has avoided compulsory redundancies by giving individuals genuine options, crucially protecting our most vulnerable members for whom dual location arrangements were not suitable on account of their exceptional circumstances.
“Santander deserves credit for recognising its responsibilities to its employees and I hope other employers follow the moral lead the bank has taken in what is likely to be one of the first of many far-reaching corporate readjustments to the post-Covid world of work.”