More than 20,000 people from 191 countries applied for the two-year program that expects to raise their profile as role models for civic engagement.
The former president spoke to the Fellows at Stony Island Arts Bank in the city's Grand Crossing neighborhood, while the former First Lady also held meetings with high school students on the city's South Side.
"Learn from each other, share experiences, and support each other," Pres. Obama said.
The Fellows program was designed to bring together leaders from around the world who are "creating transformational change on many of the world’s most pressing problems," the foundation said in a statement.
Through the program, the Fellows will collaborate with one another across a variety of disciplines, developing personalized plans to "take their work to the next level," according to the foundation.
Two of this year's Fellows hail from Chicago, which the Obamas themselves call home - and where the Obama Presidential Center is slated to be built. A third participant was raised in Chicago and now lives in Los Angeles. The others are from New York, California, Haiti, India, Rwanda and Greece.
Tiana Epps-Johnson and Dominque Jordan Turner were the two Chicagoans selected to participate.
"I see talent and greatness every time I look at the city of Chicago," Jordan-Turner said. "Unfortunately, it doesn't match the narrative that you hear on the news about young people in the city."
Epps-Johnson works for the Center for Technology and Civic Life, "improving voter turnout by training elections officials to better communicate with voters," while Turner works with the organization Chicago Scholars to help "under-resourced youth to get to and through college" and "find meaningful careers."
The Fellows selected for the program had never met the Obamas, and they were thrilled to get the opportunity.
"This was a really exciting day," Epps-Johnson said. "I'm looking forward to having the chance to talk about how we develop as leaders and how we deepen our thinking about issues."
All 20 Fellows were selected in the last six weeks and arrived in the Chicago area Sunday - spending two days at Starved Rock State Park for a team-building exercise before meeting the Obamas for the first time on Wednesday for the roundtable discussion on the city's South Side.
Wednesday's event marked the first of four "multi-day gatherings" scheduled to take place over the course of the two-year, non-residential program - for which a new class will be selected each year.