TJ Lane, 19, is serving three life sentences after pleading guilty to the murders.
Police said another prisoner, convicted robber Clifford Opperud, had also escaped in the same incident.
Authorities said they do not believe the men are armed but they are both considered dangerous.
A third inmate had briefly escaped before being recaptured, police spokesman Andy Green said.
The mother of one of TJ Lane’s victims said she was fearful when she heard the news of his escape.
“I’m disgusted that it happened. I’m extremely scared and panic-stricken. I can’t believe it,” said Dina Parmertor, whose son Daniel, 16, was among the dead.
Police said they would notify parents at Chardon High School of any decision to close the school by Friday morning.
The other escaped prisoner, 45-year-old Clifford Opperud, was serving a sentence for aggravated robbery, burglary and kidnapping, police said.
“Officers are currently searching the neighborhoods in the vicinity of the north end of town,” a police statement said.
Aircraft were being used to search for the escaped prisoners, Lima police said in a Facebook post.
Police said they were notified of prisoners’ escape from the Allen Oakwood Correctional Institution at 20:00 local time.
TJ Lane pleaded guilty last year to three counts of aggravated murder, two counts of attempted aggravated murder and one count of felonious assault.
He used a .22-calibre pistol to fire 10 shots at a group of students in Chardon High School’s cafeteria, killing Demetrius Hewlin, 16, and Russell King, 17, as well as Daniel Parmertor.
Three others were wounded in the attack, which took place when TJ Lane was 17.
Despite evidence he suffered psychosis and hallucinations, TJ Lane was found competent to be tried as an adult.
During his trial, TJ Lane smirked and smiled as victims’ relatives spoke. During his sentencing he wore a T-shirt with the word “Killer” written on it.
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