The Thrift Shop star and the U.S. leader will "openly share their own experience with substance use as they discuss the scourge and stigma of addiction" in the one-hour documentary MTV's Prescription For Change: Ending America's Opioid Crisis.
"(The documentary will highlight) some of the things we need to do to address this epidemic," a statement from Macklemore reads. "I'm one of millions of Americans who has struggled with addiction and abused pain killers, and if it weren't for treatment and recovery I wouldn't be here today."
The world premiere of the documentary on 11 October (16) will take place at the White House in Washington, D.C. in conjunction with the South by South Lawn festival.
Following the premiere of the documentary, a panel featuring MACklemore and other guests will be moderated by MTV News Senior Political Correspondent Ana Marie Cox.
The documentary featuring the rapper and President Obama will debut on MTV later this year (16), alongside a programme about transgender youth in Los Angeles and a docu-series about Major Lazer's groundbreaking concert in Havana, Cuba.