Based in the former House of Fraser store, Flannels boasts more than 200 designer brands for men, women and children - from established international designers to contemporary labels.
Monday’s opening marks the biggest luxury retail investment to date in the city, according to the company, with around £10 million spent transforming the 55,000 sq ft space ahead of its grand opening.
Michael Murray, FLANNELS’ Group head of elevation, said: “We’re confident we are introducing a truly world-class offering to Sheffield, and a beauty concept that disrupts the traditional.
"Continually ripping up the rule book and looking at retail spaces in a different way, this store will be the go-to luxury destination in the North.”
The brand already has an outlet at Shirebrook in Derbyshire.
The company has agreed a 15-year lease at Meadowhall Scroll down for a first look inside.