"In the enduring struggle between democracy and tyranny, I know where I stand and I know where the United States belongs," Harris said, accusing Trump of bowing down to dictators.
On the final, and most anticipated, night of the four-day Chicago convention, Harris, 59, promised to chart a "new way forward" as she and Trump, 78, enter the final 11 weeks of the razor-close campaign.
Kamala Harris said she would defend US interests and warned that dictators "are rooting for Trump". (EPA PHOTO)
Harris emerged as the Democratic candidate little more than a month ago when allies of President Joe Biden, 81, forced him to quit the race.
It was a forceful speech for a candidate who, during her brief campaign, had yet to articulate much of her vision for the country and faced a stream of personal attacks from Trump, who mocked her Black and South Asian heritage and called her weak on the foreign stage.
After days of protests from Palestinian supporters who were disappointed at not getting a speaking spot at the convention, Harris delivered a pledge to secure Israel, bring the hostages home from Gaza and end the war in the Palestinian enclave.
"What has happened in Gaza over the past 10 months is devastating. So many innocent lives lost, desperate hungry people fleeing for safety over and over again," she said.
"The scale of suffering is heartbreaking."
The election was a "precious, fleeting opportunity" to move past divisiveness, Kamala Harris said. (EPA PHOTO)
"President Biden and I are working to end this war such that Israel is secure, the hostages are released, the suffering in Gaza ends and the Palestinian people can realise their right to dignity, security, freedom and self-determination."
In some of her strongest foreign policy statements to date, Harris said she would take whatever action was necessary to defend US interests against Iran and would not cosy up to tyrants and dictators.
She said such leaders, including North Korea's Kim Jong-un, "are rooting for Trump".
Trump, who had promised to respond to Harris's speech in real time, posted a series of messages on Truth Social as she spoke about him, including: "She stands for Incompetence and Weakness - Our Country is being laughed at all over the World!" and "She will never be respected by the Tyrants of the World!"
Harris described the November 5 election as a "precious, fleeting opportunity to move past the bitterness, cynicism and divisive battles of the past".
Kamala Harris was joined by husband Doug Emhoff along with running mate Tim Walz and his wife Gwen. (AP PHOTO)
"A chance to chart a new way forward."
She drew a series of contrasts with Trump, accusing him of not fighting for the middle class, planning to enact a tax hike through his tariff proposals, and having set in motion the end of a constitutional right to abortion with his picks for the US Supreme Court.
She noted the Supreme Court's recent ruling about presidential immunity and the risks that would engender if Trump gained power again.
"Just imagine Donald Trump with no guard rails," she said.
Harris told delegates she would pass an income tax cut that would benefit more than 100 million Americans, and said she would fight for abortion rights, voting rights legislation, boosting the housing supply and banning what she has called "price gouging" by grocers.
Vice-President Kamala Harris and second gentleman Doug Emhoff embraced after her speech. (AP PHOTO)
Her campaign has also proposed raising the corporate tax rate from 21 per cent to 28 per cent.
Before the speech, thousands of Palestinian supporters once again gathered to protest US support for Israel as it wages war in Gaza.
The issue is one of the most divisive among Democrats and got little attention at the convention, which could hurt Democrats at the polls.
Harris has raised a record-breaking $US500 million ($A744 million) in a month and narrowed the gap or taken the lead against Trump in many opinion polls of battleground states.
Nationwide, she leads Trump 46.6 per cent to 43.8 per cent, according to a compilation of polls by FiveThirtyEight.
