She was the first Ptolemaic queen known for certain to rule in her own right, and thus first confirmed female Pharaoh of Egypt since Tausret's reign during New Kingdom period.

[6] In 169–168 BC, the siblings' maternal uncle Antiochus IV of Syria invaded Egypt.

Ptolemy VI Philometor briefly joined Antiochus IV outside Alexandria in 169 BC, then turned against him in alliance with his siblings.

Antiochus IV was finally induced to give up his attempt to take over Egypt by Roman intervention.

Ptolemy VIII had retained the allegiance of parts of Egypt and gradually expanded his control from there.

The latter was unable to offer effective support to his mother-in-law, as Ptolemy VIII pitted against him a rival for the Seleucid throne.

Among amnesty decrees seeking to heal the conflicts stirred by the recent civil war, Cleopatra II's murdered son Ptolemy Memphites was deified as the God Neos Philopator in 118 BC.

At the wishes of the Alexandrians, Cleopatra III chose Ptolemy Lathyros, her elder son, as her co-ruler.