The man, who has not been named, offloaded several rounds at Mammoth Cave, in Kentucky, after telling other overnight visitors the half-man-half-ape had lunged at him.
Park rangers have since said they had found no evidence Bigfoot was there – but are investigating the fact a firearm was fired.
Madelyn Durand and Brad Ginn, who reported the incident, said the shooter had woken them at 11pm on Sunday by shining a flashlight in their tent.
"We got out and saw a man [and his son] who told us their campsite had been destroyed by someone or something," said Ms Durand, 22. "We heard them coming back about 10 minutes later. We heard them yelling 'I see it'.
“We saw the flash from his gun, and he shot maybe 20 yards from the side of our tent into the pitch-black darkness."
Asked if she was scared, the Western Kentucky University student told CNN: "I was mostly just concerned about him shooting the gun in the middle of the night without him really seeing anything.”
The couple called 911 and decided to hike the five miles back to their car without staying the night, she added.
It is unclear what happened to the shooter but park spokeswoman Molly Schroer said rangers knew who he was and that no threat remained in the area.
Although US laws prohibit the discharge of firearms in national parks, she said no charges had been brought as yet.
The incident comes just eight months after a Montana man reported being shot at in a forest by a gunman who then told him he had mistaken him for Bigfoot.
The legendary creature, also known as Sasquatch, is more commonly associated with America’s Pacific Northwest region but sightings have been reported all over the country.