Eric Pickles has decided Peel's huge Liverpool Waters development can go ahead without need for a public inquiry.
The planning application for the scheme was approved by Liverpool City Council one year ago this month and referred to the Communities Secretary for central government's decision.
The plans include 9,000 homes and 3m sq ft of commercial development in 150 acres of the Central Docks north of Pier Head.
Lindsey Ashworth, development director of Peel, said: "This is a well-deserved reward and justice for all those who never gave up supporting this scheme. It's our Government wishing a Happy New Year to Peel and Liverpool. A big thanks goes to the people of Liverpool who have been behind us all the way.
"English Heritage together with the World Heritage Body UNESCO put up massive obstacles to prevent this development proposal getting permission.
"Their studies and arguments have all collapsed and rightly so as it's simply not right to expect derelict parts of cities with such a rich history to stand still and be fossilised.
"This consent will open up opportunities and new prospects to link our UK businesses with other international businesses such as Asia.
"All Cities in the UK have to compete with each other and each has to compete with rival European Cities.
"Liverpool is now well placed to be alongside the best of the best. For Central Docks securing this planning permission is the end of the beginning and the start of another exciting phase of its life that will add to the beauty of Liverpool's Waterfront and the economic strength of the Liverpool region."
The neighbouring Wirral Waters was approved earlier than Liverpool Waters and was also not called in for public inquiry. Both were designated Enterprise Zones by Government in March 2011.
Peel was advised by Planit IE, Peter de Figueiredo, Winckworth Sherwood, Egerton Lea Consulting, Chapman Taylor Architects, WYG, JMP, and Colliers Destination Consulting.