The recently refurbished, 106-bedroom property is currently owned by asset management and property development firm the London and Devonshire Trust.
It will be the first Welsh venue for Macdonald Hotels & Resorts since the 2006 sale of the former Macdonald Holland House Hotel, now the Mercure Cardiff Holland House and Spa, in the Welsh capital.
Chris Gillett, managing director of Macdonald Hotels Management Services Ltd, confirmed there were no plans at present to incorporate the Macdonald brand into the Swansea venue.
"The Dragon Hotel is a modern, extensively refurbished city centre based hotel with appeal to the corporate, conference and leisure markets," said Gillett.
The hotel, which features four meeting and conference spaces as well as health and leisure facilities, is expected to develop its business guest offer under the new management deal. It was recently refurbished at a cost of £3.5m.
"This management agreement enables us to re-establish our presence in the Welsh market and to add real value to the hotel’s business – and in particular its corporate market," added Gillett.
"Macdonald Hotels & Resorts now looks forward to working with the management team of The Dragon Hotel to further enhance its market appeal and profitability in the months ahead," he added.
The West Lothian-based firm, founded in 1990, now operates 45 owned and managed hotels across the UK and Europe and ten resorts.
Its managed venues benefit from merged distribution channels, joint sales and marketing support and cost savings by working as a group.
The group, which earlier this month reported pre-tax profits of £1.9m for the year ending 29 March 2012, has recently invested significantly in its F&B offering including teaming up with Alan Murchison's 10 in 8 fine dining group and chef Jeremy Wares.
The Dragon Brasserie at the Swansea Macdonald Hotels & Resorts venue is one of a number of food and beverage options at the hotel and has been recognised with an AA Rosette.