Clinton said that the first priority of the US president was to maintain strong national security.
However, Edwards said that Clinton had abetted "neocons" in a senate vote to designate Iran's Revolutionary Guard as a terror group.
The Las Vegas debate came seven weeks before the Iowa caucus, the vote which marks the beginning of the state-by-state battle by Democrats and Republicans to select nominees for the presidential election in November 2008.
Clinton was under pressure after her campaign team accused her rivals of "piling on" her in the last debate.
However, Clinton's opponents continued to criticise her in the Las Vegas discussion, in an attempt to bolster their own campaigns and close the gap on her.
"She says she will bring change to Washington, while she continues to defend a system that does not work, that is broken, that is rigged and is corrupt," Edwards said.
Obama said Clinton was unable to give clear answers on certain issues, referring to her difficulty in explaining why she did not support driver's licences for illegal immigrants
"What the American people are looking for right now is straight answers to tough questions, and that is not what we've seen out of Senator Clinton on a host of issues," Obama said.
Other candidates in the debate criticised the strategy by some candidates of launching attacks on rivals.
"Let's stop this mud-slinging," Bill Richardson, governor for New Mexico, said.
Chris Dodd, Connecticut senator, said the "shrillness" in the Democratic presidential debates would hurt the party when it reached out to independents and Republicans in the general election.
"When a campaign is about turning up the heat or who's angrier or who's yelling louder, the American people turn off," he said.
Clinton, who has proposed a health care plan that mandates universal coverage, was critical of Obama and Edwards' records on health care.
She said Edwards did not support universal health care when he ran for president in 2004, and said Obama's health care plan would leave about 15 million Americans without cover.
"There is a big difference between Senator Obama and me. He starts from the premise of not reaching universal health care," she said.