Before an audience of foreign policy experts, candidates were probed on domestic and foreign issues including defence cuts, Iran and border security.
The latest debate put former House Speaker Newt Gingrich in the spotlight after a recent surge in opinion polls.
The first Republican nominating contest will be on 3 January 2012 in Iowa.
Mr Gingrich is the latest in a series of Republican contenders to join former Massachusetts Governor Mitt Romney at the top of the polls.
Analysts say the conservative Republican base is dissatisfied with the prospect of Mitt Romney as their nominee, and has been searching instead for a known conservative candidate capable of taking on Barack Obama in November 2012.
With few of the candidates boasting significant foreign policy experience, the latest debate offered a new challenge for the leading contenders.
Mr Romney criticised the defence cuts triggered by the failure to reach a deficit-reduction deal and mounted a strong defence of Israel, while Mr Gingrich and Texas Governor Rick Perry both spoke out on the emotive issue of immigration.
Mr Huntsman found more speaking opportunities than usual, but Herman Cain, a confident voice on domestic economic issues, was less prominent than in recent debates.
The likelihood of almost $1tn of defence and domestic spending cuts, now in prospect after Congress' failure to reach a deficit deal, was roundly criticised by most candidates.
Mr Romney said the potential costs of Mr Obama's healthcare bill matched the level of cuts to the Pentagon budget.
"We need to protect America and protect our troops and our military and stop the idea of Obamacare," he declared.
Mr Perry, once seen as Mr Romney's chief rival but whose campaign gaffes have seen him lose support, said Defence Secretary Leon Panetta should resign in protest at the cuts his department could face.
Mr Gingrich, though, took a contrasting view. "It's clear that there are some things you can do to defence that are less expensive," he said.
On Pakistan, Mr Perry and Michele Bachmann sparred over US involvement with Islamabad.
Mr Perry said he would "not send them a penny" as the country has shown the US "time after time they can't be trusted".
Ms Bachmann cautiously said she would continue sending aid to Pakistan, because they were still sharing intelligence. Pakistan, Ms Bachmann said, was "too nuclear to fail".
But Mr Romney described Pakistan as being in need of urgent development. "We need to bring Pakistan into the 21st Century - heck, into the 20th Century."
There were few sharp exchanges between candidates in the debate, which was staged and moderated by CNN.
In a rare back and forth, Mr Huntsman and Mr Romney argued about the planned US troop drawdown in Afghanistan.
Mr Huntsman said US troops should come home sooner than planned, with some acting as trainers to the Afghan army and a "drone presence" maintained in the country.
Mr Romney disagreed, arguing that leaving Afghanistan early would leave it open to more violence. The two former governors also argued over the president's role as commander-in-chief.
On Iran, Mr Gingrich said Tehran's leaders could be gone within a year if fuel supply to the government was restricted. A peaceful change of government in Iran would be vastly preferable to a war or military strikes, he said.
Mr Romney also said that his first international trip as president would be to Israel, to show US support for its long-term Middle Eastern ally.
On the question of the Arab Spring, Mr Huntsman said the US "did itself a dis-service" by acting too soon in Libya.
"Our interests in the Middle East is Israel and preventing from Iran from going nuclear," he said.
Mr Perry, who declared support for a no-fly zone over Syria earlier in the day, appeared to soften his line somewhat, saying it was just one of several actions that could be taken against the Assad regim
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