Parks police Lt. Patrick Moriarty told the Buffalo News calls came in around 10 a.m. that someone had gone over the U.S. Falls.
By afternoon, no body had been spotted and police were interviewing a witness, he said.
Unlike the Canadian Horseshoe Falls just to the west, the U.S. Falls have significant boulder build-up at the base, and Moriarty said chances of survival were slim.
"But we've got to keep looking," he said. "We're trying to keep our eyes on the water now."
The incident happened 24 hours after a man in his 40s jumped into fast-flowing Niagara River from the Canadian side and plunged 170 feet into the gorge, the Niagara Falls Review reported.
The man was in serious condition in Hamilton, Ontario, after firefighters rappelled down the steep gorge and hoisted him in a rescue basket with a crane.
Niagara Parks Police Sgt. Chris Gallagher said none of the man's personal information would be released as it was an attempted suicide.
He is only the fourth person known to have survived going over the Horseshoe Falls unprotected.
In three weeks, tightrope daredevil Nik Wallenda is scheduled to walk across the Niagara Gorge.