The Democratic frontrunner said Mr Trump was unfit to be president and his election would be a “historic mistake”.
The star of the US Apprentice hit back, saying Mrs Clinton “no longer has credibility – too much failure in office”.
Outside Mr Trump’s rally in San Jose, California, anti-Trump protesters clashed with his supporters in one of the worst such confrontations so far. Several Trump supporters were punched, one was pelted with eggs and others were spat at, reports said.
But in a boost for Mr Trump, US House Speaker Republican Paul Ryan said he would back his candidacy. He previously refused to back Mr Trump and his support is the latest sign Republicans are unifying around him. He wrote in a newspaper: “We have more common ground than disagreement”, and attacked Mrs Clinton: “A Clinton White House would mean four more years of liberal cronyism.”
In her speech Mrs Clinton, who is fighting Bernie Sanders for the Democratic nomination, rejected Mr Trump’s foreign policy points, and called him thin-skinned, irrational and unprepared. She defended the Iran nuclear deal and said a Trump presidency could start overseas wars and ruin the US economy.
“This isn’t reality television, this is actual reality,” she said.
Mrs Clinton’s address will likely ease the concerns of Democrats who feared their candidate may be unable to go toe-to-toe with the unconventional Trump, political analysts said.
They said her speech seemed crafted to try to draw in independents and disaffected moderate Republicans who are concerned about Mr Trump’s “bluster”. While his supporters have repeatedly said they like his tough talk, Mrs Clinton is betting the broader electorate will not.