The crowd rose to their feet, and delegates called out, "We love you Michelle!" after a speech that was the most well-received at that point in the night.
At another point, Obama grew emotional reflecting on Clinton's potential to be the first woman president in the country's history.
"Because of Hillary Clinton my daughters can now take for granted that a woman can be president of the United States," she said, her voice breaking with emotion.
Earlier, the party struggled to find unity in its opening night, even while attempting to highlight the diversity of its members and the platform of its nominee, Hillary Clinton, and make the case against Donald Trump.
A series of testimonials and videos put Trump's most divisive and controversial moments on the national stage. A woman with disabilities derided him for comments that were widely seen as an effort to mock a disabled reporter; a young woman with undocumented parents talked about her fear of deportation; a satirical video mocked the various Trump-branded products that were made overseas.
They were followed swiftly by testimonials of Clinton's work, highlighting her advocacy for undocumented immigrants, for health care, and for LGBT rights.
The opening night programming was carefully crafted to highlight a party unified around a platform of economic and social policies for families and diversity - especially in contrast with the Republican convention, which was held last week in Cleveland.
Among those scheduled to speak later in the night are Sen. Elizabeth Warren, D-Mass., and Vermont Sen. Bernie Sanders.
Yet minutes after the gavel went down in the Wells Fargo Convention hall, Sanders supporters made their displeasure with the party's nominee known.
They booed loudly at virtually every mention of Clinton's name and at other times, defiantly led chants of "Bernie! Bernie! Bernie!"
Behind the scenes, the Sanders and Clinton campaigns rushed to quell the anger within the Sanders ranks that had been reignited with the release of hacked emails of Democratic National Committee officials in the past week.
As the night progressed, a parade of speakers, including lawmakers, labor leaders and even pop stars, turned more fully toward making the case for Clinton and against Trump.
The rowdiest of delegates was temporarily calmed by a series of speakers who declared loudly that Clinton opposed the "job killing" Trans-Pacific Partnership trade deal. Others peppered their speeches with Spanish and highlighted stories of overcoming difficult odds.
Their testimonials were interspersed with carefully crafted videos promoting Clinton's work on health-care reform and her promise to address immigration reform.
"Valiante, brave. That's what Hillary Clinton called me when I told her I was worried about my parents being deported," said 11-year-old Karla Ortiz. "Hillary Clinton told me that she would do everything she could to help us.
"She told me that I didn't have to do the worrying because she would do the worrying for me and all of us."
Between speakers, old clips of Trump's interviews and speeches played through the convention hall.
"I don't want to sound too much like a chauvinist, but when I come home, and dinner is not ready, I go through the roof," he said in one clip.
Later, Clinton's campaign chairman John Podesta declared: "He is too erratic dangerous and divisive to entrust with the White House."
Just as it seemed that the convention floor had calmed, comedian Sarah Silverman, a Sanders supporter, and former comedian and current U.S. Sen. Al Franken, D-Minn., a Clinton supporter, teamed up to jovially encourage the two camps to unite.
"This past year, I've been feeling the 'Bern'," Silverman began. Then she said, "Hillary is our Democratic nominee, and I will proudly vote for her."
But as she vouched for Clinton, Sanders supporters began booing.
"Can I just say to the 'Bernie or Bust' people, you're being ridiculous!" Silverman retorted, touching off a volley of "Hillary!" and "Bernie!" chants.
It was just such a moment, as the convention approached its prime-time hours, that Democrats had hoped to avoid.
In an emailed message sent to his delegates just as the convention began, Sanders urged them not to sabotage the movement they had spent months building.
"Our credibility as a movement will be damaged by booing, turning of backs, walking out or other similar displays," Sanders said in the note.
After being heavily criticized by Sanders and other prominent party leaders, ousted DNC Chair Debbie Wasserman Schultz faced the prospect of boos from Sanders supporters and instead of gaveling in the convention, she remained off stage. She was replaced by Baltimore Mayor Stephanie Rawlings-Blake who opened the convention at 4:15 p.m.
But Wasserman Schultz's absence did not appease Sanders supporters for long.
For three-full hours, they objected nearly every time a motion was brought up for a voice vote, calling instead for a roll call; they chanted against the TPP trade deal; they waved signs and banners.
The leak of emails that showed DNC staff apparently scheming to help Clinton win the Democratic primary looms over the four-day convention. Wasserman Schultz resigned her post effective the end of the event. The FBI said it was investigating the breach.
Sensing a raw mood among his supporters, the Sanders team reached out to the Clinton team Monday afternoon to voice worries that its supporters may cause a stir Monday night, even after Wasserman Schultz resigned, according to a Democrat familiar with the talks.
Clinton aide Marlon Marshall and Sanders deputy campaign manager Rich Pelletier huddled in the afternoon to develop a joint plan to try to avoid excessive disruptions, the official said. This person spoke on the condition of anonymity.
Sanders sent out a signed text message to some supporters that reads: "I ask you as a personal courtesy to me to not engage in any kind of protest on the floor. Its of utmost importance you explain this to your delegations - Bernie," the official said.
The Clinton and Sanders camps have also proactively merged their floor whip teams, and Sanders surrogates - including former NAACP President Ben Jealous - will be urging Sanders supporters to not cause a ruckus on the floor.
On the convention stage, one of Sanders's most ardent backers, Maine state Rep. Diane Russell, urged his supporters to celebrate a real victory: the "unity commission" that would recommend cutting back the number of superdelegates that were not bound to vote for a nominee based on the results of the primaries or caucuses.
"We did not win this by selling out," Russell said. "We won this by standing up.
"We won this by standing together," she added.
But moments later, when Clinton supporter and Maryland Rep. Elijah Cummings rose to speak about his experience and the legacy of the civil-rights movement, hecklers rose to chant "No TPP!" No TPP!"
As the party prepared to transition to a new party chair, there were already signs that fresh efforts were underway to extend an olive branch to Sanders.
Top DNC officials released a new statement offering a "sincere apology" to Sanders for the "inexcusable remarks" expressed in the leaked emails.
Longtime Democratic strategist and a vice chair of the convention, Donna Brazile, was named interim chair of the party effective on Friday, upon the resignation of Wasserman Schultz.
On Monday afternoon, Brazile acknowledged the rowdy convention atmosphere but said she was confident that the party would get through it.
"It takes time to heal, time to come together," Brazile said. "I'm confident that we can find common ground, which is what's most important."
She added that she has been apologizing to Sanders and his campaign officials.
"We're bigger as a party than this," she added. "I've told them that we will make sure our system gets better, make sure our practices get better and make sure our email gets more secure. I've been in this party for 40 years, we love this party, and we're going to do what needs to be done."
Meanwhile, Sanders pledged to push for greater unity in his remarks later in the night, regardless of the strong feelings that remain among his supporters.
And Clinton officials said they expect that there will be a roll-call vote of all 50 states and that Sanders will have his name placed in nomination.
"We anticipate there will be a roll-call vote tomorrow night and that every vote will be counted, that we'll go through all 50 states," said Clinton campaign spokesman Brian Fallon. "We're happy to have it."