The problems have also seen Graeme Russell, the driving force behind the centre's success, hand in his notice.
CUBE's troubles date back to when the Hodder gallery ran £60,000 over budget on its completion in 1994, and the collapse of a rescue package put together with the North West Development Agency last summer.
But Russell, together with trustee David Rudlin, said the centre's difficulties could also be blamed on a lack of support from CABE, its government sponsor agency.
Over the past decade, observers have considered CUBE one of Britain's most successful architecture centres. Its latest exhibition, '100 chairs - 100 years', has seen 1,500 visitors a week, 80 per cent from outside the architecture profession.
However, this success will soon come to an end. 'CUBE in its current form will cease to exist,' Russell told the AJ. 'There will be a space of sorts, but it won't be run by us.
'CABE is not interested in the work we are carrying out. They are keen on our outreach programme and the work we do with the community, but it always felt like they had no interest in the gallery.
'It really is exceptionally sad,' Russell added. 'CUBE is very exciting and has had a series of successes over the last few years.'
Russell has also won the support of Rudlin. 'The charity will be closing down and we will not have any control over the gallery,' he said, adding that the rest of the space was 'up for grabs'.
'It will probably continue to be called CUBE, but will be in the hands of the city council. It seems likely to become something of an offshoot of Urbis,' Rudlin continued.
'CABE never saw the point of the gallery and were never keen to back it. They never seemed to get how it fitted in. This has definitely been the most successful architecture centre and it's bad news that it's closing.'
But CABE has denied it contributed to CUBE's downfall. 'We are in the middle of a two-year funding deal with them, so I can't see how it could be our fault,' said policy and communications director Matt Bell.
'There is some doubt over the need for an architecture centre in Manchester, but we are sure the city needs one. The only question is whether it should be CUBE or not,' he added.