Setting the foundation of her case for tougher foreign policies, Rice asked: "Where does America stand?"
"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," she said.
Overlooking the criticism that Bush administration drew for invading Iraq over claims of weapons of mass destruction, Rice said: "It has been hard to muster the resources to support fledgling democracies and to intervene on behalf of the most desperate."
"I know it has not always been easy though it has been rewarding to speak for those who otherwise do not have a voice. The religious dissident in China, the democracy advocate in Venezuela, the political prisoner in Iran."
"Dictators in Iran and Syria butcher their people and are a threat to regional security. Russia and China prevent a response, and everyone asks, where does America stand?"
"We cannot be reluctant to lead and you cannot lead from behind," Rice said.
Speaking about the growing budget deficit and foreign trade policies, Rice said "abandoning the field of free and fair trade...will come back to haunt us."
"If you are worried about the rise of China, just consider this -- the United States has negotiated -- the United States has ratified only three trade agreements in the last few years, and those were negotiated in the Bush administration," she said. "China has signed 15 free trade agreements and is in the progress of negotiating as many as 18 more."
Turning her attention to domestic issues, Rice warned about the state of education. "Today, today, when I can look at your zip code and I can tell whether you're going to get a good education, can I honestly say it does not matter where you came from, it matters where you are going? The crisis in K-12 education is a threat to the very fabric of who we are."
Rice, who spoke without a teleprompter and with the occasional help of her notes, received a resounding ovation from the delegates at the convention.
In a poll currently active on the Wall Street Journal's blog, more than 80 percent respondents gave an "A" to Rice for the speech, which the Washington Post's E.J. Dionne Jr. praised as "more presidential than any other speech on Wednesday night."
In an interview with CNN's Hala Gorani earlier Wednesday Rice discussed her stance regarding arms supply to the Syrian rebels, criticizing America's "muted" response to the Syrian crisis.
"I think the United States should be participating in...the arming of those rebels, because we have to remember, and you know this region as well as anyone, there are regional agendas by the outside powers that are essentially confessional agendas. Sunnis arming Sunnis, Shia arming Shia. The United States and Europe bring a more balanced approach to the region. And so, yes, we should be participating in it."
"I do think that this is a time when people are questioning American leadership," she said, adding: "I think there was a hope that if we were quieter, people would join us. Well, actually, that doesn't seem to be the case. We have the president of Egypt going to China as his first stop. When has that been the case? And so I think it's a combination of too muted a voice and also our troubles here at home."