The Clydesdale and Yorkshire banking group (CYBG) is closing 79 branches with the loss of 400 jobs.
The Unite union said the closures represented a third of the bank's branch network.
The move was described as the largest-ever closure plan by the bank.
Unite national officer Rob MacGregor said the move would be "concerning" for local communities which would be left with less choice in banking services.
Mr MacGregor said: "Staff across the Clydesdale and Yorkshire Bank will be devastated to learn that 79 branches will close and consequently over 400 colleagues will lose their jobs.
"Unite is clear that the closure of a third of the bank's branches will not only be concerning for staff but the local communities which will see their bank branch close. This cost-cutting plan leaves customers with less choice for local banking.
"The union has called on the bank to give a commitment to mitigate compulsory redundancies where possible and that they will reconsider closing any bank branches that are the last bank in a town."
He added: "Unite workplace representatives will be able to assist members over the coming day and weeks to support staff impacted by this announcement."
Clydesdale said the move had been prompted by the trend towards electronic banking.
It said the banking industry in the UK had seen bank visits fall by a third since 2011.
Unite has published a list of the branches expected to close:
- Clydesdale Bank - Aberdeen Riverside, Aberlour, Aboyne, Alloa, Banff, Bathgate, Bearsden, Beith, Bellshill, Brechin, Buckie, Cambuslang, Castle Douglas, Cumnock, Dalkeith, Dunoon, East Kilbride Stuart Street, Edinburgh Leith Walk, Edinburgh University, Forfar, Fraserburgh, Giffnock, Glasgow Aikenhead Road, Glasgow Bath Street, Glasgow Charing Cross, Grangemouth, Johnstone, Leith, Leven, Mintlaw, Renfrew, Rosyth, Rothesay, Saltcoats, South Queensferry, Stonehaven, Stranraer, Thurso, Tillicoultry and Troon.
- Yorkshire Bank - Alfreton, Barnoldswick, Bradford West Bowling, Burton-Upon-Trent, Chadderton, Cleveleys, Clitheroe, Coalville, Crewe, Filey, Gateshead, Goole, Guisborough, Hinckley, Hull Hessle Road, Knottingley, Leamington Spa, Leeds Central, Leeds Chapel Allerton, Leeds Headingley, Leeds Woodsley Road, Leigh, Middlesbrough Berwick Hills, Newark, Normanton, Norton, Nottingham Bulwell, Ossett, Pickering, Retford, Richmond, Ripon, Royton, Sheffield Broomhill, Sheffield Firth Park, South Shields, Todmorden, Wath upon Dearne and Wellingborough.
A statement from the bank said: "The Bank continues to reshape its service offering in response to these changing needs.
"To support this transformation the Bank is committing £350m over the next two years, embracing digital innovation while continuing to invest in a more sustainable branch network to deliver a superior customer experience.
"The Bank's first priority is to our customers and we will be working extensively with impacted customers, local communities and relevant stakeholders to ensure that the transition to their new branch is as smooth and as sensitive as possible, particularly where vulnerable customers are concerned.
"It is also the Bank's intention to try to find roles for frontline branch staff either within other branches or elsewhere in the Bank, wherever possible."
Clydesdale customer banking director Gavin Opperman added: "While the decision to close any branch is never an easy one, it is important that we, in line with other banks operating in the UK market, continue to respond to changes in the way customers want to bank with us.
"The changes announced today continue our journey towards a model that combines an enhanced digital platform with a right sized branch network; allowing customers to interact with us through a wide range of channels - mobile, online, telephone, in-branch - whenever and however they want."