Both inmates are white men who records show had been held at Baldwin State Prison, a facility about 160km southeast of Atlanta, and they were being transported between Hancock State Prison and Georgia Diagnostic and Classification Prison. State officials said there were 31 other inmates on the prison bus.
Teresa Slade, a spokeswoman for the sheriff's office, said authorities did not know where the inmates were heading.
"We're not sure," she said. "We have the direction that they fled, and we have a very wide net with all the surrounding counties. But the direction's unknown."
The Georgia Department of Corrections identified the inmates as Donnie Russell Rowe, 43, who was sentenced for aggravated assault, and Ricky Dubose, 24, sentenced for armed robbery.
Officials urged anyone who sees the two men to contact police.
"Our hearts are heavy as we mourn the loss of two of our officers, who are our family, and our priority is to locate these fugitives and bring them to justice for this heinous act against those working to protect the public," Gregory Dozier, commissioner of the Georgia Department of Corrections, said. "We are utilising full resources of our local, state and national partners and appreciate their support."
A spokeswoman for the corrections department identified the two guards as Christopher Monica, 42, who was hired in 2009, and Curtis Billue, 58, who was hired in 2007. Both men worked as correctional officers at Baldwin State Prison, she said, and the department said they had an "unwavering commitment to their job" and their families.
According to police in Athens, Georgia, the inmates committed a burglary in Madison, Georgia, and changed out of their white prison clothes.
