The Sinn Féin representative was speaking for the first time since First Minister Peter Robinson withdrew support for the project earlier this week.
Mr McGuinness told a republican gathering at Balinamore, Co Leitrim, on Saturday evening that the move could jeopardise jobs and the peace process.
He said: "This week's decision by the DUP to abandon the agreement reached on the future development of the Maze/Long Kesh site is a mistake.
"It is a mistake not just because it jeopardises much needed investment and jobs, but also for the message it sends to the vast majority of people - nationalist and unionist - who are rock solid behind the peace process."
Political unionism needs to realise that nothing can be gained by continually feeding the insatiable appetite of those who see life through a red, white and blue prism.
Martin McGuinness, SF
Mr Robinson wrote a letter to his party colleagues on Thursday stating that the dramatic move followed "the behaviour of Sinn Féin", amid fears amongst victims and unionists that the proposed reconciliation centre would become a "shrine to terrorism".
A watchtower, H-block cell and prison hospital where 10 republican hunger strikers, including Bobby Sands, starved to death in the early 1980s have been preserved.
Mr McGuinness, who was speaking at a memorial parade for veteran republican John Joe McGirl, suggested that the DUP's u-turn is against the spirit of the Good Friday Agreement.
He continued: "Some in the extremes of political unionism believe that they can unpick the Good Friday Agreement. Moves like this give them succour. They are violently opposed to this process because at the heart of it they are opposed to equality.
"History is littered with unionist leaders who made this mistake."
Reacting Lagan Valley DUP MLA Edwin Poots hit out at what he called Mr McGuinness's "woeful lack of leadership".
These remarks made at a Republican commemoration demonstrate Martin McGuinness doesn't get the damage he and his party have done and doesn't seem to care.
Edwin Poots, DUP
"The absolute hypocrisy and cheek of Martin McGuinness knows no bounds," Mr Poots said.
"He needs to stop blaming everyone else for the action taken on the Maze and wake up to the reality that his party and their actions are responsible for the lack of confidence that any Peace Centre can be a shared space."
Meanwhile, North Belfast DUP MLA Nelson McCausland said the party believes "the rest of the Maze development can and should proceed without obstruction".
"The decision regarding the peace centre does not need to impact upon the massive economic potential of the site and the thousands of jobs which can flow as a result. The only people who appear to be casting any doubt on these jobs are Sinn Féin," he said.
SDLP leader Alasdair McDonnell said the latest comments continued to "sour the political process".
"This public fighting does nothing to aid or assist the ordinary people of the north who we were all elected to serve," he said.
"All it does is to sour the political process and make the challenging and necessary decisions that we as political leaders face all the more difficult."
Meanwhile, the board of the Maze/Long Kesh Development Corporation has called for clarification on the issue amid the fresh political row.
A statement from chairman Terence Brannigan said: "During today's scheduled meeting of the Maze Long Kesh Development Corporation, board members discussed amongst other matters issues relating to the Peace building and Conflict Resolution Centre. The board agreed to ask the First Minister and deputy First Minister to urgently clarify the situation."
The future of the former prison site outside Lisburn, which housed many paramilitary prisoners during the Troubles, has sparked much debate since it was closed 13 years ago.
The Prison Officers' Association has called for the remaining buildings to be levelled.