In a statement the Cornwall-based group confirmed the closure, adding that the site would be taken over by The Taphouse. It also suggests the restaurant's team will be taken on by the new owner.
Called Rick Stein's Fish and located on Falmouth's Discovery Quay, the restaurant launched in 2010 and was Stein's first opening outside of Padstow.
The statement reads: "A message from Rick about the closure of Falmouth: ‘I am very happy that The Taphouse has taken over our wonderful site and team in Falmouth.
"As we opened our first ‘nationwide restaurant’ in the summer; Stein’s At Home, bringing our simple, easy to cook, dining experience into homes across the country, our teams need to work on growing this area further to ensure we ‘pandemic proof’ the company and our other restaurants for the future."
In June last year the group closed its restaurant in Porthleven as part of a restructure of its estate.
The site was subsequently acquired and relaunched by chef Michael Caines as The Harbourside Refuge.
A second Stein restaurant, in the Wiltshire town of Marlborough, was also set to shutter last year, but was eventually saved from closure by its landlord.
The Rick Stein Group now operates 10 restaurants across the UK, including its flagship The Seafood Restaurant in Padstow.