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 Waitrose food store 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.
“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 and 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.”