"Imagine him in the Oval Office facing a real crisis," the former US secretary of state and first lady said, as she accepted the Democratic nomination for president early on Friday.
"A man you can bait with a tweet is not a man we can trust with nuclear weapons."
Mrs Clinton took the stage to roaring applause from flag-waving delegates on the final night of the Democratic convention in Philadelphia, relishing her nomination as the first woman to lead a major US political party.
But her real audience was the millions of voters watching at home, many of whom may welcome her experience, but question her character.
She acknowledged those concerns briefly, saying: "I get it that some people just don’t know what to make of me."
But her primary focus was persuading Americans to not be seduced by Republican presidential candadate Mr Trump’s vague promises to restore economic security and fend off threats from abroad.
Mrs Clinton said the US needed a leader who would work with allies to keep America safe.
The presidential election presented a stark choice on national security, she said, with the US facing "determined enemies that must be defeated".
She said people wanted "steady leadership", vowing to stand by Nato allies against any Russian threats.
And she pledged to defeat the Islamic State group with air strikes and support for local ground forces, while authorising a "surge" in intelligence to prevent terrorist attacks.
"We will prevail," she said.
She also said she was proud of the Iran nuclear and global climate agreements and both must be enforced now. Neither deal happened while she was in government.
Mrs Clinton’s four-day convention began with efforts to shore up liberals who backed Bernie Sanders in the Democratic primary and it ended with an outstretched hand to Republicans and independents unnerved by brash billionaire Mr Trump.
A parade of military leaders, law enforcement officials and Republicans took the stage ahead of Mrs Clinton to endorse her in the general election contest.
"This is the moment, this is the opportunity for our future," said retired Marine general John Allen, a former commander in Afghanistan.
"We must seize this moment to elect Hillary Clinton as president of the United States of America."
American flags waved in the stands of the packed convention hall. There were persistent, but scattered calls of "No more war", but the crowd drowned them out with chants of "Hill-a-ry" and "U-S-A!"
Mrs Clinton now has just over three months to persuade Americans that Mr Trump is unfit for the Oval Office and overcome the visceral connection he has with some voters in a way the Democratic nominee does not.
She embraced her reputation as a studious wonk, a politician more comfortable with policy proposals than rhetorical flourishes. "I sweat the details of policy," she admitted.
Mrs Clinton’s proposals are an extension of President Barack Obama’s two terms in office: tackling climate change, overhauling the nation’s fractured immigration laws and restricting access to guns.