US Defence Secretary Donald Rumsfeld was repeatedly interrupted and heckled by anti-war protesters during a speech.
One protester, retired CIA analyst Ray McGovern, accused Mr Rumsfeld of lying to the American people about the presence of WMD in Iraq before the war.
Mr Rumsfeld rejected the accusation and said the Bush administration based its assertions on existing intelligence.
The outbursts were more severe than the previous protests Mr Rumsfeld has faced over the Iraq war, correspondents say.
It comes weeks after Mr Rumsfeld was called upon to resign by six retired senior US military officers for his handling of the war.
The defence secretary was giving a speech on military alliances in Atlanta, Georgia, when he was interrupted by hecklers, including one who carried a sign saying: "Guilty! of war crimes".
Three protesters were escorted away by security, while a fourth stood in the middle of the room with his back to Mr Rumsfeld in silent protest, the Associated Press reports.
Mr Rumsfeld waved away his security guards when he was confronted by Ray McGovern, a former CIA analyst of 27 years and an outspoken critic of the war.
"Why did you lie to get us into a war that caused these kind of casualties and was not necessary?" Mr McGovern asked him.
Donald Rumsfeld faces mounting pressure over the Iraq war
"I did not lie," Mr Rumsfeld replied.
He said he, the then Secretary of State Colin Powell and President Bush each spent "weeks and weeks with the central intelligence people" before making their case for war.
"I'm not in the intelligence business," the defence secretary went on, amid continued questioning by Mr McGovern.
"They gave the world their honest opinion. It appears that there were not weapons of mass destruction there."
A woman who said her son was a US soldier who died in Iraq asked if the Pentagon was making sure US troops were better equipped for combat, Reuters news agency reports.
"You bet," he replied. "And I'm so sorry about your son."