It will see a concessions building belonging to the centre being demolished, with the supermarket being built to the rear of the garden store, formerly the Wyevale Garden Centre.
There will also be a new storage building to serve the garden centre as well as alterations to vehicle access and service roads.
The project, due for completion by next autumn, could create 120 jobs.
Waitrose, part of the John Lewis Partnership, has included detailed reports on air quality and lighting, as well as a 50-page dossier on the ecological and bio-diversity impact of the project.
The 15,000 sq ft store would have parking for 450 cars and 18 trolley bays.
Waitrose carried out a public consultation and 96 per cent of the 250 people who responded were in favour.
Of these, 72 per cent expressed full support and 24 per cent highlighted support, but with some reservations. Four per cent objected to the plans.
Nigel Keen, director of development, said: "We have worked in partnership with the Garden Centre Group to prepare an application we are confident will be welcomed by the local community.
"As well as creating new jobs, it will provide residents with a convenient, high-quality food store that will stop them having to travel out of the area to carry out their shopping.
"We’ve been encouraged by the positive feedback received so far."
Northampton Borough Council’s planning committee will consider the application, possibly at early as its January meeting.