The government-driven project aims to unlock millions of dollars of private sector investment and create thousands of direct jobs in the region over coming decades.

"Today is the start of a journey that will continue over the next few generations ... it's a game-changer for this region," Deputy Premier John Barilaro said at the project's launch on Thursday.

The precinct's focus will be the creation of a national and international defence, aerospace and advanced manufacturing hub, which, in-turn, will generate future investment and employment opportunities in the region.

It will build on $11.79 million defence, aviation and technology commercial precinct (Astra Aerolab) adjacent to Williamtown airport.

BAE Systems, which is part of the existing precinct, is supporting the Australian Air Force's growing fleet of F-35 Joint Strike Fighter aircraft.

It estimates F-35 sustainment activities will see about 400 jobs created over the next 10 years and remain at this level over the 30 plus year contract.

BAE Systems Australia director of aircraft sustainment and training Andrew Chapman said the announcement of the Special Activation precinct further supported the push for Williamtown to become a pre-eminent aviation, defence and aerospace-related manufacturing hub.

"Our company has invested heavily in the development of bespoke aerospace capabilities, developing our people and supporting our supply chain to ensure the RAAF has the capability it needs," he said.

"Now more than ever government and industry collaboration is needed to build on the foundations established in the region to support sustainable growth in the Hunter Valley."

As a first step in establishing the Williamtown precinct, the state government has allocated $5 million to create a precinct masterplan over the next two years.

The government will also streamline planning approvals and tailor infrastructure investment in areas such rail, roads and drainage to support the precinct's establishment.

Billions of dollars worth of related infrastructure projects, such as a rail link from Hexham to the airport and the extension of the airport's existing runway to accommodate international planes and the Newcastle freight bypass are also likely to eventually flow from the precinct's establishment.

The establishment of a rail link to the airport would increase the pressure to build the long-awaited Hexham to Fassifern freight bypass project.

The proposed Newcastle Airport runway extension and terminal upgrade, which have been among the region's top infrastructure priorities for the past decade, would open up the airport to wide-body long-haul international aircraft.

An independent economic impact assessment for the project found spending $150million on the upgrades would boost regional economic income by $12.7billion over the next 20 years and create 4,410 new full-time jobs in the region that otherwise wouldn't have been achieved through natural airport growth.

Mr Barilaro said the project would "absolutely" be considered as part of the planning process.

"I know there has been a lot of conversation about the runway extension but you can't just isolate one item, one piece of the puzzle.

"That's why the special activation precinct will look at master planning this whole region and we will revisit the runway as part of the masterplan going forward." Mr Barilaro said on Thursday.

Newcastle Airport chief executive Peter Cock said the precinct would ensure the region was capable of attracting global investment and jobs.

"Our region is already an economic powerhouse for the nation, but there is greater potential yet to be realised. The airport is a vital enabler and is ready to play a strong role in the region's future aspirations and prosperity," he said.

"We've had recent and positive discussions with the federal government regarding the runway upgrade and feel there is genuine acknowledgement of the importance of the project and a real desire to deliver a great outcome for the region.

"This is a once in a generation opportunity. If the Code E upgrade is not completed now as part of the RAAF's scheduled maintenance works, it will a massive opportunity lost."

In addition to infrastructure, the precinct's 10,000 hectare footprint is likely to take-in part of the PFAS-contaminated red zone surrounding the RAAF base.

"The initial investigation is the land acquisition and what parts (are needed) and this may become a remedy for some parts of the land that has been contaminated," Mr Barilaro said.

"We have always identified this as an opportunity and we will look at all those opportunities going forward."

Special Activation Precincts have already been created at Parkes, Wagga Wagga, Moree and the Snowy Mountains from the $4.2 billion Snowy Hydro legacy fund.

"Special Activation Precincts are about making it easier and more attractive for businesses to set up in regional NSW, create more jobs and grow our regional engine industries such as freight and logistics, renewable energy, advanced manufacturing, agribusiness, tourism, hospitality and defence," Mr Barilaro said.

"This is about attracting more money to regional NSW, creating job and career opportunities for locals and people who are keen to relocate and cutting red and green tape to support job growth in the wake of COVID-19 , bushfires and drought."

Newcastle Lord Mayor Nuatali Nelmes said the precinct formed part of the Greater Newcastle Metropolitan Plan.

"It is important to recognise that that cities and regions are a mix of many different working parts and those parts work in tandem and play off each other," she said.

"This announcement and the flow-on effect to the supply chain is of high value to this region."

Port Stephens deputy mayor Chirs Doohan said the council had been pushing for the establishment of the precinct for many years.

"This is the culmination of 20 years of hard work and planning by a whole bunch of Port Stephens council staff to try and boost the economy in this area," he said.

"The impact of COVID-19 to this area has been devastating. The effects to our tourism and travel industry, there will be no coming back from some of this, but this a shot in the arm that will ensure the economy will remain stable and take us into good stead into the future,"

The Hunter Business Chamber also applauded the announcement.

"The declaration will help the region realise the huge potential that exists in having Australia's premier defence flight base and one of its fastest-growing regional airports within the one precinct," Chamber executive Bob Hawes said.

"This announcement reinforces the importance of the Williamtown precinct to the state.

"We hope it will boost the airport's efforts to seek funding for a runaway expansion and terminal upgrade that promise further economic uplift through increased freight and tourism opportunities."

Property Council Hunter Regional Director Anita Hugo said the Williamtown precinct would be a significant driver of new jobs and investment for the Hunter.

"The streamlining of planning approvals and provision of certainty for investors will allow Williamtown to more quickly realise its potential as a world class centre for defence and aerospace innovation, as well as establishing itself as a key freight and logistics hub for Northern NSW," Ms Hugo said.

"Newcastle Airport is a global gateway to our region and we should be supporting its growth and upgrade as a critical player in that precinct."

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