Prince Harry, Gloria Estefan, and Chance the Rapper are among the names attending the two-day Chicago summit.
The British royal will address the roughly 500 young civic leaders and community activists chosen from 20,000 applicants from around the world, for what the Obama Foundation promises will be intensive workshops and opportunities to share ideas.
Chance the Rapper and Estefan will perform in a public concert to cap the event.
The gathering in the Obamas' hometown is being organised by their eponymous foundation, which is also building the former president's library in the Midwestern US city where Obama got his political start.
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Among the attendees highlighted by the foundation was Trisha Shetty of India, who started the organisation SheSays to combat sexual abuse against women.
Other notable speakers was Matteo Renzi, the former Italian prime minister, and Hamdi Ulukaya, founder of the Chobani yogurt brand.
Chance the Rapper, a socially active hip-hop artist who was born and raised in Chicago, was helping to organise the concert finale.
"I want to help inspire and empower young people to change their world," the artist said in an email released by the foundation.
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