Prison inspectors Dame Anne Owers and Dr Michael McGuire said Maghaberry Prison was so bad the safety of inmates was at risk.
Maghaberry prison is one of the most expensive in the United Kingdom and also one of the worst, a team of inspectors have said.
They have listed 200 ways to make the jail better and called for urgent action and better safety procedures.
Inspectors who made a surprise visit to the jail in January called it one of the UK's worst performing prisons.
The January inspection came six months after an inmate hanged himself while under supervision in a specialist unit.
The report by Criminal Justice Inspection NI and Her Majesty's Inspectorate of Prisons, which was published on Tuesday, said Maghaberry was one of three jails out of 169 inspected which was particularly poor in the area of safety.
It said the jail failed to meet standards in all four of the internationally recognised tests for prisoner welfare.
This is the third damning report on Maghaberry this year. A new governor took over the running of the prison on Monday.
The report again pointed to poor working practices and tense industrial relations as holding back progress.
An inmate hanged himself while under supervision in Maghaberry
BBC NI Home Affairs correspondent Vincent Kearney said: "In terms of overall performance, it is in the bottom third despite being one of the most expensive prisons in the UK with an annual cost of £81,500 per prisoner.
Prisons minister Paul Goggins said he was "disappointed" at the report's findings.
But he welcomed the steps already in place to improve the prison.
"Whilst there are many dedicated and hard working staff at Maghaberry, there is substantial room for improvement and I have already made clear to the new governor that there has to be a step-change in the way the service is delivered at this prison," he said.
Details of the latest report were published by Dr Michael Maguire, chief inspector of criminal justice in Northern Ireland, and Dame Anne Owers, HM chief inspector of prisons in England and Wales.
Dr Maguire said he was "disappointed" that of 155 recommendations made after the last major inspection of the prison in 2006, more than half - 54%- had not been achieved in the three years since.
He said the prison had "serious operational deficiencies that will require a concerted effort to change".
At the time of the inspection, inspectors found:
• There was no local suicide or self-harm policy for the prison
• There was little therapeutic support for some very vulnerable men
• Poor monitoring procedures were in place for those at risk
• Too little attention was paid to anti-bullying and investigating violent incidents
• The Standby Search Team within the prison still had too forceful a presence
• Its activities were not subject to sufficient independent monitoring
"Inspectors were also concerned at the lack of activity places to keep prisoners purposefully engaged which led to many men spending most of their days locked up without the opportunity to gain useful skills," said Dr Maguire.
The director-general of the Prison Service, Sir Robin Masefield, said he accepted the need for change.
"I'm not denying it is a disappointing report and I accept the criticisms for that," he said.
"But what I am saying to you is what we need to see is a step-change in Maghaberry's performance. I am very confident that with the team and working in unison with the staff... we can make those changes that we all want."