Condemning the prison as a legal "no man's land," Obama told a White House news conference that it was time Congress agreed to shut the jail and said the military was trying to keep starving detainees alive.
"I continue to believe we have to close Guantanamo. I think it is critical for us to understand that Guantanamo is not necessary to keep America safe," he said, in reponse to a reprter's question on the hunger strike.
"It is expensive. It is inefficient. It hurts us in terms of our international standing. It lessens cooperation with our allies on counterterrorism efforts. It is a recruiting tool for extremists.
"It needs to be closed," he said.
His words were the toughest the president has delivered on Guantanamo for months and reflected his frustration with Congress, which he blamed for blocking his efforts to shut the jail during his first term.
A spreading hunger strike among inmates, who are protesting their indefinite detention without charges or trials, has put Guantanamo back in the headlines and placed Obama in a difficult position.
The U.S. president said it was "not a surprise to me" that there were "problems" at Guantanamo.
Out of 166 inmates held at the prison at the remote U.S. naval base in southeastern Cuba, 100 are now on hunger strike, according to the latest tally from military officers.
And of those, 21 detainees are being fed through nasal tubes.
The military has sent extra medical staff to cope with the hunger strike, which is entering its 12th week.
"I don't want these individuals to die," he said. "Obviously, the Pentagon is trying to manage the situation as best as they can, but I think all of us should reflect on why exactly are we doing this."
Obama has long argued for prosecuting enemy combatants in civilian courts and transferring those cleared of wrongdoing to their home countries.
As a candidate in 2008, Obama pledged to close the jail and announced plans to close Guantanamo immediately after entering office in 2009.
But a majority of lawmakers, particularly Republicans, have insisted the jail should stay open, that the detainees are too dangerous to hold on the U.S. mainland and that the suspects should only be tried before military tribunals.
"The President faces bipartisan opposition to closing Guantanamo Bay's detention center because he has offered no alternative plan regarding the detainees there, nor a plan for future terrorist captures," Buck McKeon, the Republican chairman of the House Armed Services Committee, said in a statement.
Obama said he would try again to persuade Congress to find a way to close the prison, which was set up by his predecessor, George W. Bush, to hold those captured in Afghanistan and elsewhere after the attacks of September 11, 2001.
"I'm going to reengage with Congress to try to make the case that this is not something that's in the best interest of the American people. And it is not sustainable."
Obama warned the situation would only get worse and said it made no sense to hold more than 100 people in a "no man's land" indefinitely -- even after the withdrawal of U.S. forces from Iraq and soon in Afghanistan.
It is "contrary to who we are and our interests and it needs to stop," Obama said, adding: "It is a hard case to make."
Rights groups, which have long branded the prison as a legal "black hole," welcomed Obama's remarks.
But the American Civil Liberties Union (ACLU) said Obama could take action now to transfer more than half the inmates out of Guantanamo, without waiting for Congress.
"The president can also order the secretary of defense to start certifying for transfer detainees who have been cleared, which is more than half the Guantanamo population," said ACLU Executive Director Anthony Romero.