Byrne, who oversaw the site from 2013-17, has this month agreed a deal with private investors with previous industry experience to resurrect the site.
Manchester House closed and entered administration in October, which its owner Living Ventures blamed on a period of “difficult trading”.
Byrne was rumoured to be taking on the site after he stepped down from D&D London’s 20 Stories restaurant in Manchester last month, less than a year after its successful launch.
Manchester House will reopen to the public in early December, with reservation line details to be announced next week.
“The history that connects me to Manchester House is very personal and I truly couldn’t imagine anyone else at the helm for this reinvention,” says Byrne.
“I’m hoping [the restaurant] will once again confirm itself as a staple on the Manchester dining scene, exactly where it belongs.
“Manchester House has always been about pushing the boundaries, delivering a unique fine dining experience and staying true to that endeavour. It belongs to Manchester, an institution in its own right and we want our customers to feel as if they belong here too.
“There will be changes to come but at the moment we are keen to get the restaurant open for trading."
Manchester House launched as a £3m project in 2013, headed up by Byrne. It was long hyped to win a Michelin star, but never received the award.