He is reported by the Georgian chronicles to have been extremely grasping and ambitious and to have had frequent conflicts with his peace-loving father, insisting that Alexander made war upon the rival Bagrationi branch presiding over Kakheti's western neighbor, the Kingdom of Kartli.
Also, he was suspicious of his younger brother, Demetre, whom Alexander had entrusted an important diplomatic mission to the Shah of Iran, Ismail I.
On April 27, 1511, George murdered Alexander, had Demetre blinded, and seized the crown.
Immediately after his accession to the throne, George II organized an expedition against Kartli, and attempted to depose King David X. David's brother, Bagrat I, Prince of Mukhrani, who led the successful defense of the kingdom, was rewarded with the castle of Mukhrani, thus founding a long-lasting branch of Bagration-Mukhraneli.
In 1513, George II made another incursion into Kartli, but was again defeated and ambushed by Bagrat's men on his route back to Kakheti.