"There's no doubt in my mind that every election is important in its own way, but I can't think of an election that was more important in my lifetime," the Democrat told thousands of supporters in the first stop of a three-day bus tour through the Rust Belt battlegrounds of Pennsylvania and Ohio.
"It's not so much that I'm on the ticket, it's because of the stark choice that's posed to Americans in this election," she said.
The anti-Trump message was a striking reminder of Clinton's own vulnerabilities, as polls show that a majority of Americans say they question her honesty. Rather than ask Americans to trust her, she implored them to rally against Trump, who she cast as dangerous and unfit to lead the country.
Trump is also targeting Ohio and Pennsylvania as states where he can make headway with blue-collar white men. That demographic has eluded Clinton and was unlikely to be swayed by a Democratic convention that heavily celebrated racial and gender diversity.
"I am watching Crooked Hillary speak," Trump tweeted during Clinton's remarks. "Same old stuff, our country needs change!"
The celebratory mood of this week's Democratic national convention continued Friday as Clinton smiled and waved as she boarded her blue campaign bus, wrapped with the slogan "Stronger Together." She took the stage at her first rally with her husband, former president Bill Clinton, and running mate Tim Kaine, the Virginia senator, standing behind her.
Set-up inside Temple's McGonigle Hall this AM for Clinton rally.Had to move event from Independence Mall due to rain pic.twitter.com/mhE8c76KOT— Katherine Scott (@KScott6abc) July 29, 2016
"I stayed up really late last night. It was just hard to go to sleep," she told supporters gathered in a West Philadelphia arena, a short hop from the arena where Clinton delivered her acceptance speech Thursday night. "It was so exciting but I have to tell you it was also kind of overwhelming. I take deeply and with great humility the responsibility this campaign imposes on us."
Clinton, accompanied by Kaine and their spouses, will use her bus trip to focus on economic opportunity, diversity and national security. Democrats hammered home those themes this week with an array of politicians, celebrities, gun-violence victims, law enforcement officers and activists of all sexual preferences and races.
Their goal is to turn out the coalition of minority, female and young voters that twice elected President Barack Obama while offsetting expected losses among the white male voters drawn to Trump's message.
"As of tomorrow, we have 100 days to make our case to America," she said.
Democrats contrasted their optimistic, policy-laden message with the darker vision and less specific platform that marked Trump's turn during the Republican convention a week earlier.
PHOTOS: The 2016 DNC in Philadelphia
Clinton's speech "was such a contrast with what we saw in Cleveland last week," Kaine told CNN's "New Day" Friday, referring to the GOP convention. He described the Republican gathering as "dark and depressing."
Kaine said "there's still an awful lot of repair work" to be done on the economy, particularly with regard to job creation. But he insisted, "We don't have a single issue in this country that we can't tackle," and said job creation would be the top priority if Clinton wins the White House.
The stakes are high: A loss to Trump would not only end Clinton's political career, it could be a devastating coda to her and her husband's political legacy and leave the Democratic Party weaker than it has been in a generation.
The convention provided hours of glowing tributes to Clinton, including deeply personal testimonials from her husband, daughter Chelsea Clinton and Obama.
And Clinton offered an open hand to backers of Vermont Sen. Bernie Sanders, her primary season rival, saying, "I've heard you. Your cause is our cause."
Throughout the convention, Democrats tried to convey the stakes of the election not only to Sanders backers but to Republicans concerned about Trump's bombastic tone and foreign policy positions.
Speaker after speaker cast Trump as intolerant, inexperienced and dangerous, including the Pakistan-born immigrant father of a Muslim-American soldier killed in Iraq, who held up a copy of the Constitution and insisted that Trump "has sacrificed nothing."
Associated Press writer Jonathan Lemire in Davenport, Iowa, contributed to this report.