Planning permission has been granted for housing, a restaurant and a Waitrose food store in Northwich Marina.
The development will be delivered by H20, a joint venture between British Waterways and Bloc.
H20 has agreed a deal with house builder McCarthy & Stone to develop 58 homes for the elderly for sale, and a restaurant.
There will be a 18,000 sq ft food store operated by Waitrose and associated parking, along with improvements to the waterways, including a new marina providing up to 40 mooring berths, and access to the waterfront, with a new cafe.
Richard Thomas, director of Bloc and development manager for H2O, said: "We are delighted that the proposals have been given planning consent so that we can now start to regenerate this long underused and mostly vacant site. We have had strong support from the local community and this is an opportunity to deliver a significant phase of the town's regeneration plans.
"It has been a real pleasure working with our partners McCarthy & Stone and Waitrose in bringing together this regeneration scheme. We also appreciate the way in which Cheshire West & Chester Council has worked with us to create a scheme which will bring a range of local benefits and look forward to finding an operator for the waterside restaurant."
Nigel Keen, director of development at Waitrose, said: "Over the years we have received many requests from local people who wanted us to come to Northwich and we have been looking for a suitable site for some time now so people don't have to travel to Altrincham or Sandbach to do a weekly shop with us. I'm therefore delighted with this decision and look forward to Waitrose being part of this important regeneration project which will bring with it significant investment and hundreds of jobs local jobs for the area."
The architects are Fairhursts and the planning consultants are HOW Planning.