The women, who were headed to Toombs County, Ga., never arrived at their destination, and have not been seen or heard from since, police said.
Opal McCannon, 78, and Phyllis Rogers, 72, were last seen in the 2800 block of Barnett Shoals Road in Athens on Tuesday morning.
They are traveling in a 2008 red Kia Optima LX with Georgia tag 981ZMK.
If you have information on the whereabouts of the women, please call Sgt. Brad Collinsworth at 706-613-3888 ext.792, or dial 911.