ITV News reports that a consultation on redundancies is due to begin this week, with 80 jobs understood to be under threat.
Brains beer has been brewed in Cardiff since 1882.
According to ITV, brewing is expected to move to England in the short term with fears for its long-term survival as a brand.
In December Brains announced all 156 of its pubs, which are mostly in Wales, would be taken over by Marston’s.
The brewery has also been put up for sale, but no buyers have been forthcoming.
Brains CEO Alistair Darby said the Coronavirus pandemic had been 'absolutely brutal' with talks beginning on closing its central brewery in East Moors, Cardiff.
Darby said talks over closing the brewery, which was officially opened by the Duke of Cambridge in March 2019, were an inevitable consequence of the investment from Marston’s.
He said: “The important thing is that the family retain ownership of the beer and brand.
“We need to work out how to perpetuate the brand, which is very important to Wales, and we are likely to need to find a new location.
“If it is brewed elsewhere, it must be of the highest quality. It must be of the finest condition.”
Marston’s announced the deal that will see it operate 156 Brains pubs in Wales just before Christmas.
The combination of leased and management contract arrangements consists of a freehold estate of 86 managed and 55 tenanted pubs, together with a leasehold estate of 15 managed pubs and bars. It employs around 1,300 people.
Marston’s already has 106 pubs in Wales but plans to continue to operate the existing 156 Brains pubs under the Brains brand.
Marston’s will operate the 141 freehold pubs on a leasehold basis from February 2021, with rent chargeable from April 2021. The majority of these will be on long lease agreements of 25 years.
The deal is set to complete in February 2021.
Marston’s CEO Ralph Findlay said the deal was a mutually beneficial transaction that safeguards the future of Wales’ leading pub company, enabling its pubs to have a stable and successful future and securing 1,300 hospitality jobs in Wales.
“This transaction is entirely consistent with Marston’s long-term strategy as a focused pub operator and strengthens our representation in South and West Wales, whilst protecting the heritage and independence of an iconic Welsh business," he said.
"These high quality pubs are a great fit with our existing estate and will benefit from Marston’s scale and operational expertise to further unlock their excellent long-term potential.
“We look forward to the pub teams joining us and to welcoming guests and the communities which they serve, back into these pubs as the country emerges from the pandemic over the weeks and months ahead.”
John Rhys, chairman of Brains, said while it wasn’t a decision taken lightly, the business is confident that both its pubs and pubs teams will thrive under their stewardship.
"This transaction enables Brains to recapitalise its balance sheet and continue its long heritage as an independent entity, preserving this great Welsh business for generations to come," he added.
"We thank all our stakeholders and our advisers, Evercore, for their steadfast support which has enabled us to achieve this transaction in these unprecedented times.”