The Co-op Group are investing what they describe as a six-figure sum to open a new food store at a former garage in Annan Road.
It is part of an £11 million plan to open 20 new stores across Scotland.
A number of new jobs will be created at the Gretna site but the exact number will not be known until nearer the opening date.
John McNeill, Co-op divisional managing director, said: “Consumer habits are changing and we know that shoppers simply want to buy what they want, when they want.
“With a store in every postal area, we’re conveniently placed to serve the needs of today’s consumers.”
The Co-op, which is a membership organisation, plans to extend its charitable activities to the Gretna area.
It will be a return to the town for the movement.
An Annan and District Co-operative Society, later Lothian and Border Co-operative, store was located in Central Avenue but closed around 30 years ago.
More recently the town’s pharmacy on Annan Road was operated by The Co-operative until changing hands more than a year ago.