Smyth, who has spent 11 years at Ramsay's three Michelin-starred site, is seeking a new location to launch her venture in autumn 2016.
Matt Abe - head chef at Restaurant Gordon Ramsay Royal Hospital Road - will continue to run the restaurant on a day-to-day basis, working closely with Gordon and group development chef James Petrie.
Ramsay said: “It’s been fantastic watching Clare develop. She is undoubtedly one of the greatest chefs to have graced my kitchen and has now become the most prominent female chef of our generation.
“It’s the right time for her to take this next step and I am thrilled to be supporting her new venture. I am also delighted that Matt Abe will now be at the forefront of Restaurant Gordon Ramsay. He is an incredibly talented young chef and I have no doubt he will rise to the occasion.”
Smyth will continue to act as consultant chef for the Gordon Ramsay Group ahead of the restaurant launch.
She said: “After 11 years, Restaurant Gordon Ramsay has been a big part of my life. I have a great fondness for the restaurant and the team, it has formed me into the chef that I am today and I am grateful for the opportunities it has given me.
“I also remain ambitious and want to build on my success. The natural way to do that is by opening my own restaurant and, with Gordon’s blessing and support, I am excited to embark on this new chapter.
“Restaurant Gordon Ramsay has always been a melting pot for amazing talent and it continues to grow and produce some of the finest chefs in the UK. Matt Abe has been working by my side for the last six years – he has real passion and an incredible work ethic and deserves this opportunity to shine”.