Ernst beat Greenfield, a non-veteran urban planner whose son serves in the Army, by more than 110,000 votes, according to The New York Times' election tracker.
"We did it! To everyone who has done so much for the campaign, thank you," Ernst tweeted after the race was called in her favor by The Associated Press. "Tonight's victory wouldn't be possible without your efforts. I'm honored by the opportunity to serve Iowa for another 6 years, and I'm excited to keep fighting for you!"
Ernst has served in the Senate since 2015, the year she retired from the National Guard after 22 years of service, including deployments to Iraq. The first female combat veteran to serve in the Senate, she is a member of the Senate Armed Services Committee.
Ivanka Trump, the president's daughter and a senior White House adviser, traveled to Iowa this week to speak to rallygoers in an effort to back Ernst. The president also spoke to her supporters in Sioux City.
"You're my kind of people," he said Monday during a rally for Ernst, according to The New York Times. "But the big congratulations comes tomorrow."
Ernst's was one of the high-profile incumbent races featuring veterans seen as a true toss-up following polls and predictors calling it for Greenfield ahead of the election.
Republicans had also hoped to secure a key race in Arizona with Martha McSally, a former Air Force pilot. But McSally lost to Democratic challenger and former NASA astronaut Mark Kelly in the state's special election.
-- Gina Harkins contributed to this report.