She fended off attacks from most of the remaining 2020 Democrats on hot-button topics including health care, automation and jobs, and taxes on the wealthy.
The fourth Democratic debate, at Otterbein University in Ohio, was the first time Warren faced the other contenders after leading a major poll.
In a Quinnipiac poll released last week, Warren led the field with 29% support among Democratic and Democratic-leaning voters. Former Vice President Joe Biden trailed her by 3 points.
The poll also did head-to-head matchups for the top three Democrats against President Donald Trump, with 49% of self-identified registered voters saying they'd vote for Warren over Trump, compared with 41% who said they'd reelect the president.
These are the five attacks from Warren's rivals that generated the biggest fireworks Tuesday evening.
1. Warren accused of being 'evasive' on raising taxes to pay for health plan
Candidates first grilled Warren on how she would will pay for her proposed health care plan.
"I have made clear… costs will go up for the wealthy and for big corporations, and for hard-working middle-class families, costs will go down," Warren said.
South Bend, Indiana, Mayor Pete Buttigieg doubled down on his criticism that Warren was been "evasive" on how the middle class would pay for "Medicare for All."
"Well, we heard it tonight. A yes or no question that didn't get a yes or no answer," he said. "This is why people here in the Midwest are so frustrated with Washington in general. ... Your signature, senator, is to have a plan for everything, except this. No plan has been laid out to explain how a multi-trillion dollar hole in this Medicare for All plan that Senator Warren is putting forward."
Warren hit back by saying that Buttigieg's proposed plan is "Medicare for All who can afford it."
"Costs are going to go up for the wealthy, they're going to go up for big corporations. They will not go up for middle class families, and I will not sign a bill into law that raises their costs," she insisted.
"I don't think the American people are wrong when they say that what they want is a choice," Buttigieg responded. "And the choice of Medicare for all who want it, which is affordable for everyone, because we make sure that the subsidies are in place, allows you to get that health care."
Sen. Bernie Sanders, who also supports Medicare for All, said, "I do think it is appropriate to acknowledge that taxes will go up. They're gonna go up significantly for the wealthy, and for virtually everybody the tax increase they pay will be substantially less than what they were paying for premiums and out-of-pocket expenses."
"At least that's a straightforward answer. But there's a better way," Buttigieg said.
Sen. Amy Klobuchar echoed Buttigieg's praise of Sanders' directness.
"I'm sorry Elizabeth, but you've not said that, and I think we owe it to the American people to tell them where we're gonna send the invoice," Klobuchar said. "I believe the best and boldest idea here is to not trash Obamacare but to do exactly what Barack Obama wanted to do from the beginning, and that's have a public option that would bring down the cost of the premium and expand the number of people covered and take on pharmaceutical companies."
Even Donald Trump's team weighed in on the discussion.
"Unable to be honest about raising taxes to pay for her healthcare plan. So obvious that she's dodging and not doing it well," Tim Murtaugh, the Trump campaign's communications director, told ABC News.
2. Warren's comment on automating jobs
Warren was also confronted with her statement that automation threatening jobs is "a good story, except it's not really true."
"The data shows that we have had a lot of problems with losing jobs, but the principle reason has been bad trade policy," Warren explained. "The principle reason has been a bunch of corporations, giant multinational corporations, who have been calling the shots on trade, giant multinational corporations that have no loyalty to America. ... They are loyal only to their own bottom line."
Entrepreneur Andrew Yang challenged her comment.
"Senator Warren, I have been talking to Americans around the country about automation. And they are smart. They see what's happening around them. Their main street stores are closing. They see a self-serve kiosk in every McDonalds, every grocery store, every CVS ...[There are] 3.5 million truck drivers in this country," Yang said. "And my friends in California, are piloting self-driving trucks. What is that going to mean for the 3.5 million truckers or 7 million Americans who work in truck stops, motels and diners that rely upon the truckers getting out and having a meal? Saying this is a rules problem is ignoring the reality that Americans see around us every single day."
Rep. Tulsi Gabbard agreed with Yang, saying the fear of automation taking jobs away is "fear that's well-founded."
"As people look to this automation revolution, they look to uncertainty," she added. "They don't know how this is gonna affect their jobs and their everyday lives."
3. A proposed wealth tax
Sen. Amy Klobuchar attacked Sen. Elizabeth Warren a second time over proposed taxes.
Warren responded to a question about whether a wealth tax would "demonize" the wealthy, saying that "an entire generation of Americans" should be put before the billionaires benefiting from paying less.
Klobuchar, asked if she believed a wealth tax was the solution, said it "could work" but said she wanted "to give a reality check, here, to Elizabeth."
"No one on this stage wants to protect billionaires. Not even the billionaire wants to protect billionaires. We have different approaches. Your idea is not the only idea," Klobuchar said to applause, referencing Tom Steyer's response that he agrees with Sen. Bernie Sanders' belief that billionaires shouldn't exist.
Warren defended her position, arguing that Klobuchar was dreaming "small," a response she has given before when attacked by a more moderate candidate on stage, and that income tax increases for the wealthy, which Klobuchar argues for, don't do enough.
"Taxing income is not going to get you where you need to be the way taxing wealth does, that the rich are not like you and me. The really-really billionaires are making their money off their accumulated wealth, and it just keeps growing," Warren responded. "We need a wealth tax in order to make investments in the next generation."
Entrepreneur Andrew Yang and former Texas Rep. Beto O'Rourke piled on with criticisms of Sen. Elizabeth Warren's idea for a wealth tax.
"Senator Warren is 100% right that we're in the midst of the most winner-take-all economy in history. And a wealth tax makes a lot of sense in principle," Yang said. "The problem is that it's been tried in Germany, France, Denmark, Sweden, and all those countries ended up repealing it, because it had massive implementation problems and did not generate the revenue that they projected."
O'Rourke accused Warrren of being "focused on being punitive or pitting some part of the country against the other, instead of lifting people up and making sure that this country comes together around those solutions."
"Senator Warren said show me your budget, show me your tax plans and you'll show me your values," he added. "She has yet to describe her tax plan. ... Under my administration, if you make less than $250,000 a year as a family, you will not see a tax increase."
Warren responded that she was "shocked at the notion that anyone thinks I'm punitive."
"Look, I don't have a beef with billionaires," she said. "All I'm saying is, you make it to the top, then pitch in 2 cents so every other kid in America has a chance to make it. That's what this is about."
4. Breaking up big tech
Yang and Harris each took aim at Warren's proposal to break up big technology companies like Facebook and Amazon.
"As usual, senator Warren is 100% right in diagnosing the problem. There are absolutely excesses in technology and, in some cases, having them divest their business is the right move," Yang said. "But we also have to be realistic that competition doesn't solve all of the problems. It's not like any of us wants to use the fourth best navigation app. That would be like cruel and unusual punishment. There is a reason why no one is using Bing today. Sorry, Microsoft, it's true."
"I'm not willing to give up and let a handful of monopolists dominate our economy and our democracy. It's time to fight back," Warren responded. "Look, you get to be the umpire in the baseball game, or you get to have a team, but you don't get to do both at the same time. We need to enforce our antitrust laws, break up these giant companies that are dominating big tech, big pharma, big oil, all of them."
Harris called out Warren after the California senator called on Twitter to suspect Trump's account.
"Senator Warren, I just want to say that I was surprised to hear that you did not agree with me that, on this subject of what should be the rules around corporate responsibility for these big tech companies, when I called on Twitter to suspend Donald Trump's account, that you did not agree," she said. "I would urge you to join me because here we have Donald Trump, who has 65 million Twitter followers and is using that platform, as the president of the United States, to openly intimidate witnesses, to threaten witnesses, to obstruct justice."
Warren responded, "I don't just want to push Donald Trump off Twitter. I want to push him out of the White House. That's our job."
Harris pressed Warren to join her in saying that Trump's account should be "shut down." Warren responded, "No."
"You can't say you're for corporate responsibility if it doesn't apply to everyone," Harris said.
5. Biden points finger at Warren: 'I got votes for that bill'
Warren was brought into a scuffle between Biden and Sanders after the contenders were asked about significant policy differences.
"I think their vision is attracting a lot of people, and I think a lot of what they have to say is really important," Biden said. "I'm the only one on this stage that has gotten anything really big done."
Sanders was the first to challenge the former vice president.
"Joe, you talked about working with Republicans and getting things done," Sanders said. "But you know what you also got done, and I say this as a good friend -- you got the disastrous war in Iraq done. You got a bankruptcy bill which is hurting middle class families all over this country. You got trade agreements like NAFTA and PNTR with China done, which have cost us 4 million jobs."
Warren pointed to legislation she worked on following the financial crash of 2008.
"I had an idea for a consumer agency that would keep giant banks from cheating people," Warren said. "All of the Washington insiders and strategic geniuses said, Don't even try because you will never get it passed. And sure enough, the big banks fought us. The Republicans fought us, some of the Democrats fought us. But we got that agency passed into law. It has now forced big banks to return more than $12 billion directly to people they cheated."
Biden interjected, saying he was the one to go "on the floor and got you votes," pointing at her.
"I got votes for that bill. I convinced people to vote for it, so let's get those things straight too," he said.
Warren quipped: "I am deeply grateful to President Obama, who fought so hard to make sure that agency was passed into law, and I am deeply grateful to every single person who fought for it and who helped pass it into law."
ABC News' Cheyenne Haslett, Sasha Pezenik, Molly Nagle contributed to this report.