Authorities are identifying the inmates as Donnie Russell Rowe, 43, and Ricky Dubose, 24. The Georgia Department of Corrections said in a tweet that people should call 911 and should not approach the men if they them.
The FBI said the two were seen getting into a "grass green," four-door 2004 Honda Civic with the Georgia license plate number RBJ-6601.
U.S. Deputy Attorney General Rod Rosenstein said during testimony before a Senate budget panel in Washington Tuesday morning that federal resources are being committed to help catch the fugitives.
"An attack on any American law enforcement officer is an attack on every American law enforcement officer and the principles we all believe in," he said.
Both men have been serving sentences for armed robbery and other crimes, according to the state agency's website. Rowe had been in prison since June 2002, and Dubose had been in prison since July 2015.
Putnam County Sheriff's Office spokeswoman Teresa Slade says the inmates escaped about 7:23 a.m. Tuesday, southeast of Atlanta. She said a witness saw the men get away in a dark green Honda.
The names of the prison guards weren't immediately released.