The Chapel Arches scheme will see more than 200 new apartments, shops, restaurants, cafés and offices, built around the York Stream.
The redevelopment will also provide underground parking, a new footbridge over the York Stream and a replacement bridge to the Hines Meadow car park.
Plans from Sorbon Estates and Shanly Homes for the site have now been approved.
Cllr Derek Wilson said: “Approval for this redevelopment is a red letter day for Maidenhead.
“It is another significant signal that we are committed to taking forward the rejuvenation of the town centre.”