WASHINGTON — If Donald Trump’s unexpected rise has been fueled by the anger seething in America’s heartland, Hillary Clinton is seeking to harness a different emotion to beat him to the White House: fear that a Trump presidency would make the world a more dangerous place.

Clinton hit that note hard Thursday, delivering a blistering takedown of Trump’s temperament and warning that the presumptive GOP nominee is unfit to be commander in chief.

“He is not just unprepared — he is temperamentally unfit to hold an office that requires knowledge, stability, and immense responsibility,’’ Clinton said. “This is not someone who should ever have the nuclear codes — because it’s not hard to imagine Donald Trump leading us into a war just because somebody got under his very thin skin.’’

Clinton also peppered her speech in San Diego with biting one-liners. “This isn’t reality television — this is actual reality,’’ she said, before turning to emphasize her extensive resume.

Billed as a foreign policy speech, Clinton’s address was the clearest articulation to date of a key theme she plans to emphasize in the coming general election battle with Trump. The sharpness of her remarks was a signal to Democrats that she is prepared to take on the presumptive Republican nominee in a more visceral way, willing to go toe-to-toe with the brash New York real estate mogul.

Trump hit back using some of his trademark tactics, firing off insult-laden tweets as Clinton was speaking.

“Bad performance by Crooked Hillary Clinton!’’ read one. “Reading poorly from the telepromter ! She doesn’t even look presidential!’’

Speaking before an array of 19 American flags, the former secretary of state notably did not mention Democratic rival Bernie Sanders, who is giving her a serious challenge in Tuesday’s California primary. Clinton instead aimed her speech at undecided voters, particularly those in crucial battleground states that will be key to her beating Donald Trump.

There she hopes to find support among moderate Republicans and independents turned off by Trump — voters like Monica Nelson, a Republican who stood outside the ballroom where Clinton delivered her speech Thursday. Nelson, initially reluctant to share her last name with a reporter out of concern her family would learn she planned to vote for Clinton, said she just couldn’t bring herself to get behind the GOP nominee.

“He’s a bully. That’s what he is.’’ Nelson said she is disgusted with the Republican Party. “Look at [Marco] Rubio, he’s apologizing to him and he was insulted. Look at Megyn Kelly.’’

Clinton’s tone toggled between stately seriousness and a humorous mocking of Trump. She spoke more slowly than she typically does on the stump, striving to show herself as presidential as she argued that Trump was anything but.

In some ways, Clinton’s speech channeled the infamous 1964 “Daisy’’ advertisement run by President Lyndon B. Johnson, which insinuated that his GOP rival Barry Goldwater could trigger a nuclear war, capitalizing on Cold War fears. The ad shows a young girl plucking petals off a daisy in a meadow, followed by the image of a mushroom cloud and Johnson’s voice intoning, “These are the stakes: To make a world in which all of God’s children can live, or to go into the dark.’’

Clinton repeatedly raised the specter that Trump could entangle the country in dangerous situations by what she described as his unstable nature.

“Now imagine Donald Trump sitting in the Situation Room, making life-or-death decisions on behalf of the United States,’’ Clinton said. “Do we want him making those calls — someone thin-skinned and quick to anger, who lashes out at the smallest criticism? Do we want his finger anywhere near the button?’’

Clinton added that voters had a historic decision to make between an America “that’s angry [and] afraid’’ led by President Trump or a country that is “hopeful, generous, and confident in the knowledge that America is great — just like we always have been.’’

She also made a point in her speech of mentioning that she had visited 112 countries as President Obama’s secretary of state. Republican foreign policy leaders have been at the forefront of GOP objections to Trump — though their efforts were unable to stop his march to the nomination.

More than 120 Republican foreign policy leaders signed onto a letter published in March that declared Trump unfit for office.

“Mr. Trump’s own statements lead us to conclude that as president, he would use the authority of his office to act in ways that make America less safe,’’ they wrote.

Some of these figures, including former Reagan State Department official Robert Kagan, have said they will vote for Clinton, so great is their fear of Trump.

“The party cannot be saved, but the country still can be,’’ Kagan wrote in a February op-ed in The Washington Post.

To that end, Clinton’s speech tried to cut through the “fog of Trump’s hyperbole’’ and could give more Republicans a reason to distance themselves from Trump, said Jim Manley, a Democratic strategist and former aide to Senator Harry Reid of Nevada, the Senate’s minority leader.

“One of his most glaring weaknesses is foreign policy and national security, and they are looking for every chance they can to exploit his utterly ridiculous views and significant lack of experience,’’ Manley said. “Hosting a beauty pageant in Russia is not exactly significant foreign policy experience.’’

Doug Heye, a Republican strategist and former spokesman for the Republican National Committee, said he’s skeptical that Clinton’s message will be effective in moving Republicans and independents toward her in a tumultuous election year that has benefited outsiders like Trump and Sanders.

“Voters are so angry with Washington right now that even good arguments against Trump may not be digested by voters,’’ Heye said. “One of Hillary’s challenges is that she embodies every attack Trump makes against Washington.’’

Nonetheless, Heye characterized Clinton’s speech as important because it turns the conversation back on an issue where Trump isn’t comfortable.

“It reassures her supporters that she’s willing to take on the Goliath in the Republican party and that would, in theory, unify Democrats,’’ Heye said. “By taking on the big bad wolf, it means for the next day we’re less likely to talk about e-mails, and she needs days where e-mails are not talked about.’’

Larry Sabato, director of the Center for Politics at the University of Virginia, said the speech should boost Democrats’ confidence that Clinton can beat Trump in November. For too many months, he said, Clinton has seemed off balance, unable to focus on Trump’s weaknesses.

“She finally did it. She clearly was enjoying it,’’ he said. That could also help her in Tuesday’s neck-and-neck primary race in California, he added.

“This is exactly what she needed. She needs for those California voters on the fence to see her as the candidate who is already battling Donald Trump and giving it to him,’’ Sabato said.

Annie Linskey of the Globe staff contributed to this story from San Diego. Victoria McGrane can be reached at victoria.mcgrane@globe.com. Follow her on Twitter @vgmac. Tracy Jan can be reached at tracy.jan@globe.com. Follow her on Twitter @TracyJan.