After an all-night hunt, at least 30 of the 48 escaped animals had been gunned down, and others were apparently captured alive. As of midmorning, officers were still hunting for a grizzly bear, a mountain lion and a monkey.
Schools closed, parents were warned to keep children and pets indoors, and flashing signs along highways told motorists, "Caution exotic animals" and "Stay in vehicle."
"It's like Noah's Ark, like, wrecking right here in Zanesville, Ohio," said Jack Hanna, TV personality and former director of the Columbus Zoo. "Noah's Ark filled with tigers and lions and all leopards and a few monkeys and whatever, and it crashes here, and all of a sudden they're out there."
Neighbor Danielle White, whose father's property abuts the Muskingum County Animal Farm, said she didn't see loose animals this time but did in 2006, when a lion escaped.
"It's always been a fear of mine knowing (the owner) had all those animals," she said. "I have kids. I've heard a male lion roar all night."
Officers in the mostly rural area about 55 miles east of Columbus were under orders to shoot to kill for fear that animals hit with tranquilizer darts would run off and hide in the darkness.
The owner of the preserve, Terry Thompson, left the cages open and the fences unsecured, releasing dozens of animals, including lions, tigers, bears and wolves, before committing suicide, said Muskingum County Sheriff Matt Lutz.
Authorities would not say how he killed himself and said no note was found. Lutz wouldn't speculate on why he committed suicide or why he went out with one last act of vengeance.
Thompson had had repeated run-ins with the law, and Lutz said the sheriff's office had received numerous complaints since 2004 about animals at the property. Thompson had gotten out of federal prison just last month after pleading guilty to possessing unregistered guns.
"This is a bad situation," the sheriff said. "It's been a situation for a long time."
Hanna said that of the three animals believed to be unaccounted for, he was most concerned about the mountain lion, because of its impressive leaping ability. He said anyone confronting these animals should not run, because they will give chase.
The sheriff said his office started getting calls Tuesday evening that wild animals were loose just west of Zanesville on a road that runs under Interstate 70. He said deputies with rifles went to the animal preserve, where they found Thompson dead and all the cages open. Several aggressive animals were near his body and had to be shot, the sheriff said.
Lutz said his main concern was protecting the public in the area, where homes sit on large lots of sometimes 10 acres. Nearby Zanesville has a population of about 25,000.
Hanna defended the sheriff against criticism that the animals should have been captured alive.
"What was he to do at nighttime with tigers and lions, leopards, going out there?" Hanna said. "In the wild this would be a different situation."
Hanna told ABC's "Good Morning America" that if an officer shot a bear, a leopard or a tiger with a tranquilizer at night, "the animal gets very excited, it goes and hides, and then we have his officer in danger of losing their life, and other people."
The preserve in Zanesville had lions, tigers, cheetahs, wolves, giraffes, camels and bears. Lutz called the animals very big and aggressive but said a caretaker told authorities they had been fed on Monday.
White, the preserve's neighbor, said Thompson had repeatedly been in legal trouble.
"He was in hot water because of the animals, because of permits, and (the animals) escaping all the time," White said. A few weeks ago, she said, she had to avoid some camels that were grazing on the side of a freeway.
At a nearby Moose Lodge, Bill Weiser said: "It's breaking my heart, them shooting those animals."
Bailey Hartman, a night manager at a McDonald's, also said it saddened her that the animals were shot. But she said, "I was kind of scared coming in to work."
Ohio has some of the nation's weakest restrictions on exotic pets and among the highest number of injuries and deaths caused by them. In 2010, an animal caretaker was killed by a bear at a property in Cleveland.
On Wednesday, the Humane Society of the United States criticized Gov. John Kasich for allowing a statewide ban on the buying and selling of exotic pets to expire in April. The organization urged the state to immediately issue emergency restrictions.
"How many incidents must we catalog before the state takes action to crack down on private ownership of dangerous exotic animals?" Wayne Pacelle, president and CEO, said in a statement.
Associated Press writers Ann Sanner and Doug Whiteman contributed to this report.