Councillors have approved plans for the £100m redevelopment of land on the south bank of the River Humber, paving the way for the creation of 5,000 jobs.
The project by Able UK will include transport depots, warehousing, a business park and hotel on 1,500 acres (607 hectares) of land at East Halton.
There will also be transport links to Immingham and the Humber Sea Terminal.
After being granted planning permission Able UK said it was "very pleased" and it hoped to start work in the spring.
Neil Etherington, the firm's group development director, said he expected 5,000 jobs would be created at the site by the time it was completed in 2020.
He said: "The development of the South Humber Bank is of national and international importance.
"This is a great place to do business, ideally placed for both UK and European markets and, with transport links set to further improve, we are well placed to take advantage of economic recovery and ensure that the Humber remains the largest tonnage port in the UK."
North Lincolnshire Council's approval of the plans is subject to more than 50 different conditions, including the protection of wildlife on the site.
Council leader Mark Kirk said: "Without a doubt this is the largest application ever presented to this council that will create thousands of jobs for local people.
"The decision today marks a significant step in realising the enormous economic potential of the South Humber Gateway."