The Union Square project, which has been divided into phases, includes 650,000 square feet of offices, 150,000 square feet of retail, 450 residential units, a Primary Health Care Trust building, a bus station, multi-storey car park, hotel and a public square as well as alterations to roads.
Muse development director Doug Finlay said: "Confirmation by Swindon Borough Council of the outline planning permission is the first significant milestone if this part of the town centre is to undergo change.
"The masterplan has regeneration at its heart and it is a genuine and vibrant extension to the town centre. It will have a positive impact on Swindon creating opportunities for a range of new businesses, inward investment, homes and new jobs."
Forward Swindon has worked with its development partners Muse, the Homes & Communities Agency and the council to progress the scheme.