The massacre began Tuesday evening when sheriff deputies arrived at a notorious wild animal preserve in Zanesville, Ohio, to see Bengal tigers, lions, bears and other ferocious animals wandering away, some headed for the highway.
Fearing the animals would scatter and terrorize the town, officers began dispatching the wildlife with their pistols.
"These animals were on the move and were showing aggressive behavior," said Muskingum County Sheriff Matt Lutz.
"There were some very close calls," the sheriff said. At times it was "almost hand to hand" combat with the animals, Lutz said.
"These are 300 pound Bengal tigers that we had to put down," he said.
During the night of chaos, an escaped lion killed a monkey, and bears and lions were charging at horses kept at the preserve, he said.
When the carnage was over, 49 animals were slaughtered, including 18 Bengal tigers, 17 lions, six black bears, a pair of grizzlies, three mountain lions, two wolves and a baboon.
View Photos of the Exotic Animals Warning: photos of the slain animals are graphic.
The animals had been released by Terry Thompson, the owner of the preserve, who then killed himself, Lutz said.
"These killings were senseless. For our guys to have to do this, it was nonsense, it was crazy," the sheriff said.
ABC News' wildlife expert Jack Hanna, who advised Lutz during the crisis, said it was especially heartbreaking to see so many Bengal tigers killed when they are on the verge of extinction. But the actions by the police saved a catastrophe, he said.
A vet shot one tiger with a tranquilizer from 15 yards away and Lutz said it "just went crazy," and started to run, so officers were forced to shoot it with lethal ammunition. Another animal that got away, described as a big cat, was hit by a car on a highway some distance away, he said.
One animal, a macaque monkey, is still missing and Lutz said it is "highly likely" that it is infected with herpes B virus.
Herpes B isn't dangerous to monkeys, but "it's very dangerous for humans," said Dr. Barb Wolfe, Director of Conservation Medicine at Ohio wildlife conservatory The Wilds.
When passed to humans the rare disease can lead to deadly brain infections, according to the National Primate Research Center in Wisconsin.
Wolfe urged the public not to approach the monkey and to call 911 if it's spotted.
During the chaos, several individuals were arrested for attempting to steal the carcass of a lion that had been killed.
Six animals were still in their cages on the 73-acre spread, and Thompson's wife returned to find at least 30 of her animals lying dead on the ground.
"She's in a state of shock right now obviously," Hanna said. "She cried on my shoulder and said please don't take my family."
The remaining living animals -- a grizzly bear, three leopards and two monkeys -- are being taken to the Columbus Zoo.
"We'll be passing a law here very shortly that she'll have to adhere to as well as the other people in Ohio," Hanna said. "It sometimes takes things like this to make things better."
Thompson, 61, was recently released from prison after serving one year on federal weapons charges. According to investigators he has been cited in the past for animal abuse and neglect.
Lutz described Thompson as "a guy who kind of kept to himself, was always willing to push the envelope a little bit."
"We feel that Mr. Thompson died from a self-inflicted wound. We also feel he had released these animals at some point. Not only were the gates open but some of the pens were open," Lutz said.