In 197 BC, Antiochus III had captured a number of cities in Asia Minor previously under the control of the Ptolemaic Kingdom of Egypt.

The Romans supported the Egyptian interests, when they negotiated with the Seleucid king in Lysimachia in 196 BC.

In line with ancient Egyptian tradition of sibling marriage, she was also named sister (Ancient Greek: ἀδελφή, adelphḗ) of Ptolemy V. A synod of priests held at Memphis in 185 BC granted Cleopatra all the honours that had been given to Ptolemy V in 196 BC (inscribed on the bilingual Greek-Egyptian Rosetta Stone).

Cleopatra also held title of vizier as one of only two known Ptolemaic queens to did so (the first one being Berenice II of Egypt).

[13] The pair were unable or unwilling to prevent the deterioration of relations with the Seleucid kingdom which culminated in the disastrous Sixth Syrian War.