The debate was hosted by ABC News at the National Constitution Center in Philadelphia. The 90-minute showdown was filled with animated zingers and tense exchanges on key policy issues facing the American people.
Who won the presidential debate? How Trump, Harris' debate performance could impact poll numbers
Harris sought to portray herself as a new generation of leadership with a track record of results, while Trump tried to paint her as a radical Democrat and continued to criticize the Biden administration.
Here are some key takeaways from the debate.
Harris put Trump on defensive early on
The vice president didn't waste any time in going on the attack against Trump.
"What we have done and what I intend to do is build on what we know are the aspirations and the hopes of the American people," Harris said minutes into the debate. "But I'm going to tell you all, in this debate tonight, you're going to hear from the same old, tired playbook, a bunch of lies, grievances and name-calling."
She later took a dig at his rallies, claiming people leave them early out of "exhaustion" as he gives long speeches that sometimes include references to windmills causing cancer or to fictional characters such as Hannibal Lecter. Trump immediately defended his events and crowd sizes, saying he has the "biggest" and "most incredible" rallies in political history.
After Trump railed against crime in the nation, Harris said she thought the comments were "so rich" coming from someone who has been criminally charged multiple times. Trump has denied all wrongdoing in each of the cases against him.
Trump continues attacks on -- Biden
Trump, who had a difficult time changing his message when Harris succeeded President Joe Biden as the Democratic Party's nominee, continued to criticize Biden and continually tried to tie Harris to Biden's record -- most notably on the economy, immigration and leadership abroad.
"She is Biden," he said. "The worst inflation we've ever had, a horrible economy because inflation has made it so bad, and she can't get away with that."
RELATED: Taylor Swift endorses Kamala Harris for president after debate vs Donald Trump on ABC
Harris, who has supported many of Biden's stances while also offering her own economic proposals, quickly responded, "Clearly, I am not Joe Biden, and I am certainly not Donald Trump. And what I do offer is a new generation of leadership for our country."
In the "spin room" with reporters after the debate, Trump continued to blast the Biden-Harris record.
"She's trying to get herself away from Biden, and she wasn't able to do that tonight," he said.
Did Harris succeed in introducing herself to viewers?
A key question heading into the debate was whether Harris would be able to define herself to voters who say they don't feel they know her or what she stands for well enough.
A recent New York Times/Siena College poll found a sizable share of likely voters (28%) and registered voters (31%) feel they need to know more about Harris as a candidate. Those numbers were even higher among independent voters: 41% of registered independents and 38% of likely voters who identified as independent said they needed to learn more about her.
Harris began her first response to a question on the economy by saying she was raised by her mother in a middle-class family. Later, she highlighted her background as a prosecutor who has taken on transnational criminal organizations. She also noted that as a senator, she was at the U.S. Capitol when it was attacked by a pro-Trump mob on Jan. 6.
She also hit on some of her signature policy proposals, including her support for reproductive freedom and economic plans like expanding the Child Tax Credit and assisting first-time homebuyers. She also noted that both she and her running mate, Gov. Tim Walz, are gun owners and wouldn't take people's guns away.
RELATED: ABC News presidential debate fact check: A look at the claims made by Donald Trump and Kamala Harris
While neither candidate went too deep into policy specifics, Harris did try to paint a clear contrast between what she is offering and what she believes Trump is proposing if elected.
"What I do offer is a new generation of leadership for our country, one who believes in what is possible, one who brings a sense of optimism about what we can do instead of always disparaging the American people," she said.
Meanwhile, Trump argued Harris is a "radical left liberal" and pressed her on some of her shifts on police funding, fracking and more since her 2019 Democratic primary campaign.
Trump still refuses to concede he lost the 2020 election
Trump tried to explain his own remarks recently in which he appeared to accept he lost the 2020 election, including his comment last week that he "lost by a whisker."
"I said that?" Trump said on the debate stage when it was read back to him.
"Are you now acknowledging that you lost in 2020?" ABC News moderator David Muir asked.
"No, I don't acknowledge that at all," he said. "That was said sarcastically."
Asked about the peaceful transfer of power, Trump did not say that he regrets anything about his actions on Jan. 6, 2021. He claimed he had "nothing" to do with what happened that day, which culminated in an attack on the U.S. Capitol.
Race comes up, but not gender
For the second time, Trump is campaigning against a woman for president. Harris' gender was not broached during the debate, though her race was.
Asked by moderators about his previous false comments on her racial identity -- including that Harris, who is Black and South Asian, "happened to turn Black" -- Trump said he "couldn't care less."
"I don't care what she is. I don't care," he said. "Whatever she wants to be is OK with me."
When pressed, Trump doubled down, saying he read that she was not Black, and then that she was.
RELATED: Harris proposes 2nd debate, Trump doesn't immediately commit
"And that's okay. Either one was okay with me. That's up to her. That's up to her," he said.
Asked for her thoughts, Harris went on the attack -- but didn't focus on herself. Instead, she focused on Trump's falsehoods about former President Barack Obama's birthplace and noted "he was investigated because he refused to rent property to Black families" to cast him as divisive and unfit.
"Honestly, I think it's a tragedy that we have someone who wants to be president who has consistently, over the course of his career, attempted to use race to divide the American people," she said. "I think the American people want better than that, want better than this."
"This is the most divisive presidency in the history of our country," Trump responded.
ALSO SEE: READ: Harris-Trump presidential debate transcript