The famed Motor Speedway has hosted MotoGP since 2008 and promoters Dorna said the decision to cancel the contract was mutual.
"This outcome reflects the best interests of both the Indianapolis Motor Speedway and Dorna Sports," said IMS president J Douglas Boles.
"The timing is right to pursue other opportunities that drive greater revenue for both the speedway and our Central Indiana economy."
The decision leaves the Circuit of the Americas in Austin, Texas, as the only U.S. round remaining on the calendar after Laguna Seca, California was dropped in 2014.
The Dutch Grand Prix will switch from a Saturday to a Sunday as previously announced.
(Reporting by Alan Baldwin, editing by Tony Jimenez)
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