The NBC show, now in its sixth season, stars Amy Poehler as ambitious and embattled public servant Leslie Knope.
The First Lady’s cameo will be in the season’s final episode titled "Moving Up" and centres on her campaign against child obesity.
Poehler joined Obama on Feb. 25 to film the cameo and to appear, as herself, at a Let's Move event in Miami.
U.S. Vice President Joe Biden made a cameo on the show in 2012 and three senators, including presidential runner John McCain and California’s Barbara Boxer, have also guest starred.
Executive producer Michael Schur told the Hollywood Reporter that he was trying toi persuade Hillary Clinton to make an appearance on the show.
"I always imagined the perfect ending to the series [which] would be a casual piece of B-roll where Leslie is walking through a building in Washington, D.C., and passes Hillary Clinton, and Hillary Clinton says, 'Leslie.' Leslie says, 'Secretary Clinton,' and keeps walking."