Sanders fired back at Clinton over the use of military force, calling her proposal for a no-fly zone in Syria a bad idea and pointing out that she had supported the Iraq war with her vote in 2002. Sanders described the invasion as "the worst foreign policy blunder in the history of the country".
But one of the highlights was the moment Sanders and Clinton found common ground over the controversy surrounding her use of a private email server while she was Secretary of State.
When Clinton said she was prepared to answer all questions about the issue but preferred to talk about the problems of the American people, Sanders said: "I think ... the American people are sick and tired of hearing about your damn emails." Clinton replied, grinning broadly: "Me too, me too." As the audience cheered, she reached out to shake hands with her rival.
Clinton and Sanders were at the centre of attention on the stage in Las Vegas, but three other candidates - former Maryland Governor Martin O'Malley, former Senator Jim Webb of Virginia, and former Rhode Island Senator and Governor Lincoln Chafee - looked to give their lagging campaigns a boost before the biggest national audience they've had all year.
O'Malley, who has been sharply critical of Clinton in his campaign speeches, was restrained as he tried to highlight his record on criminal justice, immigration and other issues. Webb said his military background makes him the most qualified to be commander in chief, and Chafee called himself a "block of granite" on issues, despite changing parties.
The first Democratic debate provided a marked contrast to those held so far for the Republican candidates. The GOP events have been dominated by personal attacks, one-liners and sniping over what frontrunner Donald Trump has said about his rivals.
The Democrats' differences were focused largely on issues and policies, though there was far more engagement than some had predicted. The debate included discussions about climate change and renewable energy, university affordability, prescription drugs, terrorism and civil liberties, and the most serious threats to US security in a world awash in conflicts.
Clinton showed why she remains the favourite for the Democratic nomination, never appearing rattled or surprised by what came at her.
Sanders kept his focus on the issues - from universal healthcare to free university and the rebuilding of the nation's infrastructure - that have fuelled his rise.
Throughout the debate, Clinton and Sanders hewed closely to the main themes of their campaign. Sanders decried wealth and income inequality and the role "millionaires and billionaires" play in funding the political process.
Clinton emphasised her commitment to middle-class families.
Yesterday's encounter was the first of six scheduled Democratic debates that will be held between now and early March. The next Democratic debate will be held on November 15 in Iowa.