She called his national security ideas a series of "incoherent rants, personal attacks and outright lies."
"This is not someone who should ever have the nuclear codes," she declared, claiming Trump could start a war just because somebody "got under his very thin skin."
Before an audience of 250 invited guests, Clinton argued that Trump is a uniquely unprepared presidential candidate, whose foreign policy views are highly malleable and subject to the whims of his moods. The address offers a preview of the type of heated rhetoric and lines of attack that sure to be on display in the fall campaign.
Trump blasted back at Clinton.
"Bad performance by Crooked Hillary Clinton! Reading poorly from the telepromter! She doesn't even look presidential!," he tweeted.
In another tweet, he said, "Crooked Hillary no longer has credibility - too much failure in office. People will not allow another four years of incompetence!"
The speech, which one Clinton aide said was the "centerpiece" of her five-day trip through California ahead of the primary on Tuesday, looked to undercut Trump's ability to woo national security-focused independent and Republican voters.
"Donald Trump's ideas aren't just different -- they are dangerously incoherent," Clinton said. "They're not even really ideas -- just a series of bizarre rants, personal feuds, and outright lies."
She continued, "He's not just unprepared -- he's temperamentally unfit to hold an office that requires knowledge, stability and immense responsibility."
And she added, "We cannot put the safety of our children and grandchildren in Donald Trump's hands. We cannot let him roll the dice with America."
In her opening her remarks, she said the election in November "is a choice between a fearful America that is less secure and less engaged with the world, and a strong America that leads to keep us safe and our economy going."
Since Trump became the presumptive Republican nominee, Clinton has directly challenged his ability to handle foreign policy issues and has taken to labeling him a "loose cannon" who will make it more difficult for the United States to operate on the global arena.
Clinton's campaign feels, because of her experience as a senator and secretary of state, Clinton will be able to use her experience to effectively hit Trump on national security.
Trump, on the other hand, has questioned her judgment about interventions in Iraq and Libya -- two conflicts Clinton backed -- but has left out the fact that he previously supported them, too.
"She doesn't have the temperament to be president. She's got bad judgment. She's got horribly bad judgment," Trump said last week. "If you look at the war in Iraq, if you look at what she did with Libya, which was a total catastrophe."
Clinton, then a senator, voted in 2002 to authorize the use of military force in Iraq. And as secretary of state in 2011, she forcefully argued in favor of military intervention to overthrow Libyan dictator Moammar Gadhafi.
Before Clinton's address Thursday afternoon, President Barack Obama struck on some similar themes in his commencement address to the Air Force Academy.
While Obama did not mention Trump, he rebutted some of the foreign policy arguments Trump has put forward -- proposals that lean toward reducing America's role in global affairs.
"As we navigate this complex world, America cannot shirk the mantle of leadership," Obama said. "We can't be isolationist. It's not possible in this globalized, interconnected world. In these uncertain times, it's tempting sometimes to pull back and try to wash our hands of conflicts that seem intractable, let other countries fend for themselves. But history teaches us, from Pearl Harbor to 9/11, that oceans alone cannot protect us. We cannot turn inward."