The children from the same family were rescued from wretched conditions with human waste all around and confined to just one room over much of the past four years, authorities say.
Some of the children were unable to speak and one - an 18-year-old who was developmentally disabled - could not even write her name, investigators said.
"Most of our livestock was kept in better conditions than the children," Vinton County Sheriff Ryan Cain said. "Just a disgusting scene."
The children's parents and two grandparents were charged with felony child endangerment, a prosecutor said.
Authorities found the children while carrying out a search warrant in an unrelated investigation, Ohio Attorney General Andy Wilson said at a news conference.
Officials said it seemed as if no one outside the family knew about the children, who weren't enrolled in school.
"We didn't know there were going to be 16 kids there," said Wilson, who was nearly at a loss for words in describing what officials found in the tiny village of Hamden that sits in one of Ohio's poorest counties.
"It's the type of thing that we're not used to seeing here in America," he said.
The sheriff said it appears the children spent most of their time in a room that was roughly 3.5m by 3.5m.
The children ranged in age from one-and-a-half years to 18 years old and included both boys and girls, officials said.
Seven were transported to hospitals in Columbus and two were flown by helicopter. One was in critical condition while some of the others were admitted for care, Wilson said.
"They looked like almost feral animals," he said. "It was terrible."
The children were in temporary custody of the Ohio Department of Jobs and Family Services.
Vinton County prosecuting attorney William Archer said the four adults were charged with second-degree felony child endangering because it involves "serious physical harm."
Gary Siders Jr., Gary Siders Sr., Christina Siders and Elizabeth Siders appeared in court on Wednesday where a judge entered not guilty pleas on their behalf and set bond at $US300,000 for each. They have not yet been assigned lawyers.
The house where the children were found sits on a road tucked away alongside a steep railroad embankment, where tracks carry rumbling trains through Hamden.
An open door revealed bits of rubbish inside while a wooden deck and the backyard were filled with discarded tyres, a high chair and other debris.
Investigators said members of the family had moved around southern Ohio over the past two decades and that it looks like they avoided setting up medical and government records.
"These folks were pretty good at hiding these kids," Wilson said.
Investigators were reviewing whether the family was reported to any children's services agencies in the past.
11°C