The Wales Millennium Centre could remain closed until April next year due to the coronavirus pandemic, putting 250 jobs at risk.
All shows have been cancelled until the end of the year following the outbreak.
On Friday, staff were told the centre would remain closed until January "at least", putting 85 permanent roles at risk of redundancy. Casual staff will also no longer be employed.
The Welsh Government said it was doing everything it could to help.
The centre blamed the "devastating impact" of coronavirus on the industry.
The centre, in Cardiff Bay, has been closed since coronavirus restrictions came into effect in March and faces losing about £20m in income.
Managing director Mathew Milsom said performances could not go ahead while social distancing measures - requiring people to remain 2m apart - were in place.
He said the centre would remain closed until January 2021, but managers would review the situation in September and may extend the closure until April.
"The coronavirus pandemic has had a devastating effect on theatres across the UK and, like many others, we have concluded that we won't be able to put performances on our stages again while social distancing measures are in place.
"Under these circumstances we can't open the theatre in a way that provides a good audience experience and that is economically viable for the centre and the producers who present their work here."
The centre, which puts on its own productions and hosts visiting West End musicals, closed its doors on 17 March when people were told to avoid gatherings and crowded places.
Productions were cancelled until the end of the year, with visiting tours of the Lion King, due to start next month, and its Christmas performances of Phantom of the Opera, called off.
The centre's main auditorium was also due to host Welsh National Opera's autumn season, while its annual Festival of Voice has also been scrapped.
The centre employs 140 permanent staff, with just over half are now at risk of redundancy.
Casual staff will also no longer be employed, meaning a total of 250 roles are affected.
The closure will also affect the 300 volunteers and freelancers who work at events and productions at the centre, which has about 1.6 million visitors every year.
Following the news, performers posted their sadness about the closure and support for staff on social media.
Les Mis actress Rhiannon Porter tweeted "my heart is so heavy", while Welsh tenor Hywel Dowsell, who was due to appear in Phantom of the Opera at Christmas, said the WMC was the "jewel in Wales' crown".
The Book of Mormon, which was due to come to the WMC in November, said all its shows had been rescheduled to October 2021.
How we take things for granted 😔 this was about a week before lockdown. Performing the songs of James Bond at @theCentre which has just announced it will stay closed until January... my heart is so heavy 💔 #SaveTheArts pic.twitter.com/7Bk00sqdvY— Rhiannon Porter (@rhiannonsarah) June 12, 2020
Very sad news. @theCentre is a Jewel in Wales’ crown. On the front of the building it says, ‘In these stones horizons sing’, words by Gwyneth Lewis. Let’s hope we can continue again soon. https://t.co/1WMuybQkd6— Hywel Dowsell 🏴 (@hyweldowsell) June 12, 2020
While many staff have been furloughed, the WMC said it could not continue to pay them after the government scheme ends.
It has lost 85% of its income and the lack of ticket sales and commercial revenue means it can only continue with a reduced team of staff, it said.
It will rely on its annual grant from the Arts Council of Wales of £3.5m to fund its work while the doors are closed.
Mr Milson said the safety of audience members, staff and performers was of "paramount importance".
"Therefore, we may have to consider extending the period of closure as government advice on mass gatherings becomes clearer over the coming weeks and months," he added.
"We are also expecting significant disruption to the availability of touring shows for years to come, as productions are being cancelled and no new shows are being created.
"Whilst we are closed, we will do everything we can to keep our artistic and charitable work going, and to ensure that we are ready to reopen as soon as is practically possible."
As well as its 1,850-seat Donal Gordon Theatre, the centre also has a 300-seat studio space, a cabaret bar, and hosts Radio Platfform, a youth-led radio station and training programme.
The wider complex is also home to the BBC National Orchestra of Wales, Welsh National Opera and National Dance Company Wales, which are unaffected by the announcement.
Reacting to the news, First Minister Mark Drakeford called for the UK government to give funding to arts organisations to help them deal with "such a bleak prospect in the crisis".
The Welsh Government said it was asking the UK government to extend the Job Retention Scheme to support companies and workers.
A UK Treasury spokesman said it had provided an "unprecedented package of support for businesses".
"Our job retention scheme has helped a million employers and protected 8.9 million jobs across the UK. We have extended it until October - meaning it will have been open for eight months and will continue to support businesses as the economy reopens and people return to work.
"As well as furloughing staff, we've introduced a wide range of other targeted support measures for different sectors, including bounce back loans and tax deferrals."