AP first called Grassley as winner of the U.S. Senate race at 10 p.m., just after Iowa's polls closed at the same time. Fox News followed shortly after.
Grassley, chairman of the Judiciary Committee, has been in the Senate since 1981.
The incumbent senator's job approval ratings dipped in popularity after Senate Republicans announced they would refuse to consider President Obama's Supreme Court nominee. Grassley has since stated the Senate will not "stonewall" Hillary Clinton's Supreme Court nominee should she be elected to the Oval Office.
In the final hours of the election, Grassley pushed FBI Director James Comey for details regarding the FBI's continued investigation into Clinton's private email server, claiming Comey did not provide enough context for the agency's decision.
Grassley has been a fierce critic of Clinton's use of a private email server during her time as secretary of state, calling for the FBI's full disclosure of information gathered during its investigation.
The incumbent led a majority of polls of the U.S. Senate race in Iowa, leading on TPM's PollTracker Average on Tuesday, 56.5 to 36.1.