In remarks that at times resembled a comedy roast, Clinton unleashed a torrent of polished zingers and one-liners to attack Trump's policies and character, suggesting Trump might start a nuclear war if elected to the White House simply because "somebody got under his very thin skin."
"Donald Trump's ideas are not just different, they are dangerously incoherent," she said to a room of supporters in San Diego, California. "They're not even really ideas, just a series of bizarre rants, personal feuds and outright lies."
Clinton, the front-runner in the race to become the Democratic presidential nominee, delivered her speech as she seeks to shift her attention to the Nov. 8 election against likely rival Trump and away from Bernie Sanders, a U.S. senator from Vermont, who is continuing his long-shot bid for the nomination.
Clinton was speaking in San Diego ahead of California's June 7 primary election.
Democratic Party leaders have fretted about how to best oppose Trump, who managed to knock out all 16 rivals for the Republican nomination in part with his uninhibited style of assailing them with personal insults. Trump revels in referring to Clinton as "Crooked Hillary" and dredging up the infidelities of her husband, Bill Clinton, the former president.
Clinton's remarks were intended in part to show she would not be cowed and that she could go toe-to-toe with him in scornful put-downs.
"He says he has foreign policy experience because he ran the Miss Universe pageant in Russia," she said as the crowd guffawed, and she suggested Trump would run the U.S. economy "like one of his casinos."
During her speech, Clinton predicted Trump, who has been deeply critical of Clinton's foreign policy record, would take to his Twitter account to insult her, and he did.
"Bad performance by Crooked Hillary Clinton!" ran one posting during the speech, which included a typo. "Reading poorly from the telepromter! She doesn't even look presidential!"
Trump has said previously that Clinton is distorting his actual policies.