Developer Livia awarded Russells the £25.5m job to build the 14-storey hotel, which will boast 330 bedrooms.
The 20-month build programme, to BREEAM Very Good standard, should see the hotel open in the summer of 2015.
Designed by Manchester architect Hodder and Partners, the façade will comprise large floor-to-ceiling glazed panels for each bedroom.
Concrete contractor Buchan will supply acid etched, stone-coloured concrete for the rest of the external façade.
Engineer Capita Symonds and mechanical and electrical contractor Vitel are also on the job.
Director Gareth Russell said: “The Manchester Motel One will be our largest hotel scheme to date and follows the successful delivery of a number of developments across the country.
“We’ve established a reputation not only for delivery of hotel schemes, but also as experts in dealing with tight sites in constrained city centre locations.
“Our major projects team has developed a methodology and a number of supplier partnerships which create genuine cost and programme savings for our clients.”
Russells is currently preparing the site and completing the demolition of the existing buildings prior to construction.