The company says it's part of a modernisation process
M&S is closing its store on the Fforestfach Retail Park in March.
All 52 staff who work at the store will be moving to nearby stores.
The company says it's part of M&S's programme to modernise its UK store estate to better meet the changing needs of customers.
A statement sent out this morning said: "M&S remains committed to serving customers in South Wales through a number of other locations including Pontardulais Foodhall, located just 200 metres away.
"In addition to selling the very best of M&S food and drink, the Foodhall gives local customers the option to collect and return their Clothing & Home orders from M&S.com free of charge.
"M&S Swansea, which is situated just under four miles away, will continue to offer customers the best of M&S as the retailer's flagship store in the area - selling "contemporary wearable style across Womenswear and Menswear, as well as offering Kidswear, Home and a large Foodhall."
Sacha Berendji, Director of Retail at Marks & Spencer, said: "We're committed to transforming M&S for our customers, colleagues and shareholders. Stores will always be an integral part of our customer experience, alongside M&S.com, but we have to ensure we have the right offer in the right locations.
"We believe these changes are vital for the future of M&S and we will continue to accelerate the programme, taking tough but necessary decisions, as we focus on making M&S special."
John Turner, M&S Head of Region for South Wales, said: "This is not a decision we've taken lightly and we understand that some customers will be disappointed by the news. We've got a great team in Fforestfach and I'm pleased our colleagues will continue to serve customers in the area from other local stores."