Scottish & Newcastle has said it is to close its Tyne Brewery in Newcastle and move operations to a new site nearby.
Newcastle Brown Ale remains ever popular in pubs across the UK
Brewing will be moved two miles away to a site at Dunston which S&N is buying from the Federation Brewery for £7.2m. About 100 jobs are to be lost.
Scottish & Newcastle said production at the Tyne Brewery was "no longer commercially viable".
In February, S&N closed its 150-year-old Fountainbridge brewery in Edinburgh as part of an ongoing restructuring.
The final closure of the 121-year-old Tyne brewery next spring will mean that the world famous Newcastle Brown Ale will no longer be brewed in the city of its name.
The combined brewing business at Dunston will employ about 170 people - the Tyne brewery currently employs 150 and Federation 130.
S&N said it wants to carry out the job losses via a voluntary redundancy scheme.
The company has already said it intends to take £45m of costs out of the UK
brewing operations over the next three years.
A spokesman for the T&G Union, which represents workers affected by the announcement, said: "We are disappointed with the news of another Scottish & Newcastle brewery closure.
"But we are assured that the major regional brands will continue to be brewed on Tyneside through the acquisition of the Federation brewery."
"This news is bad for jobs and we will do all we can to avoid compulsory redundancies when the plant closes in eight months' time," the spokesman added.
Scottish & Newcastle said that a move to the Dunston Brewery, which was built in 1979, would provide the opportunity to brew both lager and ale, as well as offer extensive packaging facilities and room for development.
Stephen Glancey, director of operations at Scottish Courage, the UK division of Scottish & Newcastle, said the move was about securing the company's future attachment to the North East and Tyneside.
"This is a sad day for brewing in Newcastle, and all our efforts will be focused on working with the trade unions to help those workers affected," he said.
"However, we announced the manufacturing review 12 months ago, and have previously closed a brewery in Edinburgh. This is the second stage.
He added: "The move to Dunston simply gives us increased capacity and flexibility, not only to increase production of Newcastle Brown, but also to produce lagers, which are today two-thirds of the market in the UK, and were not possible to make at the Newcastle brewery.
"I accept that this is sad news for Newcastle, but it is more about securing our commitment to the Tyneside and the North East in general."