The project intends to “bring back to life” the historic grounds of Worsley New Hall, an estate which adjoins the Bridgewater Canal.
RHS Garden Bridgewater could become “one of the UK’s greatest gardens” when it opens in 2019, the RHS said.
The organisation has four other gardens in its portfolio, in Surrey, Devon, Essex and North Yorkshire.
The garden is part of an RHS £100m investment programme over 10 years, which hopes to “make the UK a greener and more beautiful place”.
The 10-acre walled kitchen garden in the grounds of Worsley New Hall, which was demolished in 1949, will be restored as part of the Salford project.
Historical features will be recreated, including a tree lined garden approach and the terraces, which sit between the lake and the former site of Worsley New Hall will be recovered.
A new learning centre for schools will teach pupils about horticulture, the RHS added.
The garden, developed on the 19th-century site, aims to attract one million visitors every year.
RHS Director General, Sue Biggs, said: “We always thought it would take us a long time to find the ideal site for our fifth garden, but with its beautiful landscapes, good public transport links and outstanding location, Worsley New Hall was an opportunity we couldn’t miss.”