It was the fifth tour stop of "Oprah's 2020 Vision: Your Life in Focus," Winfrey's full-day wellness event with WW (Weight Watchers Reimagined) that had the New York venue usually holding concerts at night buzzing with bright-eyed attendees lined up as early as 8 a.m.
It marked Obama's return to Barclays just 14 months after appearing at the arena for her own sold-out tour to promote "Becoming," which has sold more than 11.5 million units worldwide and won a Grammy Award last month.
"Does this feel like déjà vu for you?" Winfrey asked. "Because you were here wearing those bad, Balenciaga gold boots!"
"Barack is like, 'Where are those boots?'" Obama said. "I was like, 'They're put away, honey. Just settle down.'"
The former U.S. president was one of the main topics discussed during the wide-ranging, hourlong conversation which, at times, had the former first lady coming off like a comedian headlining a sold-out show.
"All of the people in this room paid money to come out, to give up a Saturday...," Winfrey said before Obama chimed in with: "And as I said — ain't nobody twerking onstage."
The audience erupted in laughter.
Obama cracked more jokes when she told Winfrey that she and her husband were now empty nesters since their 18-year-old daughter, Sasha, began college last fall (Malia, 21, is a junior).
"We tried to hold it together, to get (Sasha) in the car so she wouldn't start crying, and then me and Barack, we balled like little babies. Barack gets that ugly, loud cry," Obama said, imitating his cry and earning laughs from the crowd.
"He did that at Malia's graduation," she added. "We're sitting there, and he had his glasses on and speeches are happening and we're all chatting, and we hear," she said, imitating his cry again while laughing herself.
"And I'm looking at him like, 'Are you OK?'" she recalled. "He's going to kill me."
When Winfrey asked if the energy in their home was different now that the kids are gone, Obama exclaimed: "It is so good, y'all."
"OK, you guys, get out of the gutter!" Obama added.
"Parenting takes up a lot of emotional space. And my husband was busy being president," she said as the audience cheered loudly.
"Don't we wish. Don't we wish," Winfrey said.
"Just vote y'all, that's all I'm saying," Obama continued. "Just vote."
The conversation turned slightly political, again, when Winfrey asked Obama what the next chapter of her life would entail.
"President," some audience members yelled. Others screamed, "White House!"
Obama, 56, said she didn't want to get political during the chat but that she wants to spend her career empowering young people, calling them the "next generation of leaders."
"To help them understand a broader sense of values that they can operate within because I do think that we are short on that right now, that are leaders are not paving a good path for what we want our kids to be," she said. "I'm sorry to say that. I don't want to make this political in any way."
She also opened up about her marriage, saying that going to therapy taught her that she is responsible for her own happiness.
"I didn't marry Barack for him to make me happy," she said.
"We're coming back to the point where we see each other again because some of the hardest times in our lives we just escaped it, we survived it," she added. "And we went through a tough time. We did some hard things together and now we're out on the other end and I can look at him and I still recognize my husband. He's still the man that I fell in love with."
This year the couple is celebrating 28 years of marriage.
Winfrey's event featured the mogul discussing her own wellness journey, a dance exercise from choreographer Julianne Hough, a pre-show dance party and a performance from Grammy-winning gospel singer and WW Ambassador Tamela Mann. Winfrey also honored Tara Deckert, a lieutenant in the New York Police Department, as well as her colleagues and city employees for their wellness transformation as part of the WW-WorkWell NYC partnership. One person onstage said she lost 140 pounds.
Celebrity guests in the crowd included Lupita Nyong'o, Niecy Nash, Hoda Kotb, Nate Berkus, Merle Dandridge and Winfrey's BFF Gayle King, who faced backlash this week for asking WNBA star Lisa Leslie about a sexual assault charge against the late Kobe Bryant.
Winfrey, who said in an interview Friday that King is facing death threats, sort of referenced the drama when she told the audience Saturday, "I had no peace this week."
But Winfrey put the main focus on Obama and encouraged the audience to make 2020 their year of transformation and triumph.
When the topic turned to health and Winfrey asked Obama what she appreciates about her body, she said: "It's mine. All mine. It's a healthy body that works every day and I try not to judge it."
"As a child growing up with a father with a disability who could not walk; my father would have given anything to have any one of my legs, for me to judge that and not to just embrace it and be happy that I am alive, moving, able to move, I have to tell myself: 'Appreciate what God gave you and take care of that, and be balanced about it,'" she added.
The women also discussed aging and how some people go to great lengths to try to look younger.
"And then you have all of these frozen faces," Winfrey said.
"When you're in the photo line and everybody looks the same and you're like, 'Didn't I just meet you?'" Obama said, laughing. "Y'all just have the same lips."
"And the same forehead," Winfrey replied.
"Stop it. Let it go," Obama said.
"That's pretty funny," Winfrey said, laughing in her seat. "I just met you. No I didn't."