Worsley New Hall was chosen for "its beautiful landscapes, good public transport links and outstanding location", said RHS director-general Sue Biggs. The 63ha garden is to open in 2019, as part of the society's £100m 10-year strategy to promote horticulture across the UK.
Stoke's Park Hall Country Park was on the final shortlist of two options for the flagship garden but lost out to Worsley Hall. The move was disappointing for both Stoke's council and Midlands residents who had hoped that the new garden would be more accessible for day trips.
However, the RHS is still in talks about possible investments in Stoke, with some speculation it may be considering basing one of its two planned inner-city gardens in the area. "We are still in discussions with the RHS about their interest in the city as the location for one of their new national gardens," said a Stoke council spokesperson.
"The RHS was massively impressed by the city and its community spirit. The fact that the RHS has been so enthusiastic about Stoke-on-Trent is testament to how the far the city has come recently.
"Should one of the world's most respected horticultural organisations finally decide to invest here it will attract thousands of visitors every year and focus even further attention on the city as a growth point for the nation. This is a fabulous city and big decision-makers in London are finally waking up to its potential."
Any more specific proposals would be shared with local people before a final agreement is reached, said the council.
An RHS spokesperson said: "It is the community and their energy that has been what has really excited the RHS about the city, so we expect them to put the community at the heart of anything they do. We are discussing ways with Stoke-on-Trent as to how we can expand our community outreach and education work in conjunction with them."