The pop-up will be at the West Quay Road hotel for a two-week period between 4 and 20 September.
It will be open to serve lunch and dinner for the duration of the Southampton Boat Show with the Grand Harbour Hotel providing an al-fresco Bottega Prosecco Bar to accompany it.
The menu will consist of a selection of the restaurant’s current menu including Rillettes of Duck Pruns d’Argen, Ribeye Boston style with Oysters, Maldon Rock Oysters and Wheeler’s Fish Pie.
Pierre White said: “Southampton is a beautiful harbour city and its rich maritime heritage is a perfect fit with the essence of Wheeler’s. We hope it receives a warm welcome from Sotonians and visitors alike.
“It promises to be a special few weeks.”
Laura Roberts, general manager at the Grand Harbour Hotel, said: “Thousands of people visit Southampton during the Boat Show and we have worked incredibly hard to bring Marco and Wheeler’s here at such an important time.
“Wheeler’s is a great brand with an excellent menu that reflects the standards of quality and service we want to achieve here. We are confident it will be a popular choice for visitors throughout September.”