Ptolemy Epiphanes was only a small boy when his father, Ptolemy Philopator, died. The two leading favorites of Philopator, Agathocles and Sosibius, fearing that Arsinoe would secure the regency had her murdered before she heard of her husband's death so securing the regency for themselves. In 202 BCE however Tlepolemus, the general in charge of Pelusium put himself at the head of a revolt which ended with Agathocles and several of his supporters being killed by the Alexandrian mob.

Antiochus III the Great and Philip V of Macedon made a pact to divide the Ptolemaic possessions overseas. Philip seized several islands and places in Caria and Thrace, whilst the Battle of Panium (198 BCE) definitely transferred Coele-Syria, including Judea, from the Ptolemies to the Seleucids.

Antiochus after this concluded peace, giving his own daughter Cleopatra I to Epiphanes to wife (193–192 BCE). Nevertheless, when war broke out between Antiochus and Rome, Egypt ranged itself with the latter power. Epiphanes in manhood was remarkable as a passionate sportsman; he excelled in athletic exercises and the chase.

Great cruelty and perfidy were displayed in the suppression of the native rebellion, and some accounts represent him as personally tyrannical. In 197 BCE Lycopolis was held by the forces of Ankmachis, (also known as Chaonnophris) the secessionist pharaoh of Upper Egypt, but was forced to withdraw to Thebes. The war between North and South continued until 185 BCE with the arrest of Ankmachis by Ptolemaic General Conanus.

The Rosetta Stone was a statement of thanks to the Egyptian priesthood for help during the crisis.

The elder of his two sons, Ptolemy VI Philometor (181–145 BCE), succeeded as an infant under the regency of his mother Cleopatra the Syrian. Her death was followed by a rupture between the Ptolemaic and Seleucid courts, on the old question of Coele-Syria.

This article incorporates text from the Encyclopædia Britannica Eleventh Edition