The 130-bedroom property will launch alongside a 127-bedroom Premier Inn with frontage on to East Market Street and Cranston Street.
They will be located within a £150m development which will incorporate restaurants, 28 retail spaces, homes and offices, Centred around a civic square, the development will link the city's New Street/East Market Street area and Waverley Station with the Royal Mile.
John Bates, Whitbread Hotels and Restaurants' head of acquisitions for UK & Ireland added: "This is another outstanding deal for Premier Inn. It gives us more than 257 new bedrooms in central Edinburgh and also our first new Hub by Premier Inn outside London.
"We are now set to have two great Premier Inn products side-by-side in a superb new development in the heart of the Old Town - and close to Waverley Station. It is more exciting growth for us in Scotland and another big result for our customers."
Lukas Nakos, Artisan's managing director said: "There has been huge interest in the site from hotel operators around the world, and I am pleased that an operator of Whitbread's stature and pedigree has chosen to significantly invest in the city.
Work on the development is due to start in mid-2014.