Retailer Wilko has confirmed its Stockton store in Castlegate Shopping Centre will be closing as part of plans to shut 15 outlets this year.
The firm said the affected stores would close as leases end and favourable terms cannot be agreed, adding it will not affect its new openings or its stores relocation programme.
But the GMB union said it was "another nail in the High Street's coffin", warning that hundreds of jobs could be lost.
Jerome Saint-Marc, Wilko's chief executive said: "Our history is steeped in serving our customers and communities going back to 1930 but there's no denying the way people shop with us and where they want to shop with us is changing."
He said the company would support affected staff, who would be offered any available positions in nearby stores.
Roger Jenkins, GMB national officer, branded the closures "devastating" for Wilko workers.
He added: "It's yet another nail in the High Street's coffin and GMB calls on councils and landlords to review commercial leases and offer lower rents."
Wilko said 11 of the 15 stores have an alternative within five miles.