The announcement this week came as the retailer looks to the opening of a new store in Craigavon around the same time.
No jobs are at risk from the closure, staff having been advised that all existing employees at the Lisburn branch will be redeployed.
An M&S spokesperson said the decision to close the city centre store was not taken lightly.
The company’s Northern Ireland Head of Region, Simon Layton, said: “The decision not to renew our lease and therefore close our small food store in Bow Street Mall, Lisburn was a difficult one to make.
“I understand many of our loyal customers will be disappointed and we hope to see them in our nearby Lisburn store at Sprucefield shopping complex.
“The store will close in the Autumn when we will be delighted to open our new store in Craigavon. We’ve got a brilliant team of 40 colleagues at the store who will all move to nearby stores.”
The Mayor, Councillor Uel Mackin and the Chairman of the Development Committee of Lisburn and Castlereagh City Council, Alderman William Leathem, have expressed their disappointment at the decision.
The Mayor said: “I am sorry to hear that the store will not continue trading in Bow Street Mall but I am glad to hear that redeployment will be offered to the store’s employees, and this must be welcomed.
“The M&S Simply Food store has been in the Mall for years and I am sure it will be missed by many shoppers.”
Alderman Leathem added: “I was sad to learn of this announcement, which I am sure was very carefully considered by M&S management. This is a difficult period of change for the people who work at the store. Our lives are often centred around our places of employment and our routines.
“The Council is engaged with Bow Street Mall in respect of future plans for the centre.”