Police Chief John McKeel told the media that the pair of black men ordered everyone in United Mississippi Bank to the floor and forced a teller to open the vault.
They had backpacks that they crammed with cash, then fled on foot.
McKeel said police believe an accomplice was waiting in a vehicle nearby, with the escape route being La. 105 North.
There were four employees and no customers in bank when the desperadoes entered it shortly before noon.
One suspect is described as short (5-5) and other tall (6-3).