"That is the question of the hour: Where does America stand?" Rice said. "You see when the friends or foes alike don't know the answer to that question, unambiguously and clearly, the world is likely to be a more dangerous and chaotic place."
The United States has had to address that question since World War II, she said as she answered the question with, "We stand for free peoples and free markets. We will defend and support them."
She acknowledged the burdens of leadership are heavy and it isn't always easy to speak for those who don't have a voice.
"I know it feels as if we carried these burdens long enough," she said.
But if the United States doesn't carry that burden, one of two things will happen, she said. Either no one will lead and there will be chaos, or someone will lead who doesn't share America's values.
The United States cannot afford not to lead and it "cannot lead from behind," she said.
Republican presidential nominee Mitt Romney and running mate Paul Ryan "understand this reality," she said. "They know our allies must be able to trust us ... and know we'll be reliable, consistent and determined."
America's foes also must have "no reason to doubt our cause because peace really does come through strength."
When the world looks to the United States, "they look to us because we are the most successful economic and political experiment in human history," Rice said. "That is the true basis of American exceptionalism."
The essence of America is the idea that someone from humble beginnings can do great things, she said.
"Mitt Romney and Paul Ryan have the integrity and the experience and the vision to lead us," Rice said. "They know who we are. They know who we want to be. They know who we are in the world and what we offer.
"That is why this is a moment and an election of consequence."
Earlier, Rice was interrupted twice by hecklers protesting her role in President George W. Bush's administration, during which the wars in Iraq and Afghanistan began.
In an event sponsored by the U.S. Global Leadership Coalition, Rice was interrupted as she was discussing "what could be done to show that America was compassionate about the poorest people," The Hill reported.
A woman shouted, "You cannot be compassionate and kill people."
The woman was escorted out without resistance.
A second protester, also a woman, later shouted, "The blood of American children is on your hands" and that the Sept. 11, 2001, terrorist attacks on the United States were "an excuse" to begin the war in Iraq.
The second protester was also led out.