Muse is working in partnership with Network Rail on the 2.5 acre site next to Victoria Station.
Work will see the creation of three new buildings: a 150,000 sq ft, Grade A, eight-storey office development, as well as two residential buildings of 20 and 25 storeys.
Muse will now progress the design and contractor procurement process, with construction expected to begin on site in the final quarter of 2017.
David Burkinshaw, development director at Muse, said: “New Victoria offers an unparalleled location and an outstanding development opportunity.
“Securing planning consent is a key milestone for the project. Working closely with Network Rail, Muse can now advance the detailed design of the first phase of residential.”
David Biggs, managing director of network rail property, said: “The project will help us deliver our targets to release former operational railway land for homes.
“Being given the go ahead shows clearly that Network Rail’s £44 million investment at Manchester Victoria station has provided a major catalyst for wider regeneration in the city, delivering much-needed homes and development opportunities.”
Muse is working with architect Sheppard Robson and Arup on detailed design proposals for the scheme.
Deloitte Real Estate acted as planning advisers.