She was queen consort of Syria from 150 to about 125 BC as the wife of three Syrian kings: Alexander Balas, Demetrius II Nicator, and Antiochus VII Sidetes.

In 152 BC, her father, who had come into conflict with the Seleucid king Demetrius I Soter, chose to promote Antiochus IV's son Alexander Balas against him and supported him with troops and officers.

Alexander quelled the Cilician revolt and returned home, confronting Ptolemy and Demetrius in the plain of the river Oeneparas, close to Antioch.

Demetrius repudiated his alliance with Egypt and expelled or massacred all of Ptolemy's garrisons in Syria as far as Gaza, reinstating a fragile Seleucid control over the province.

Diodotus, a former general of Alexander and probable participant in the Antiochene rebellion, abducted Cleopatra's first son Antiochus VI and used him as a figurehead for a secessionist kingdom in Coele-Syria.

During these years of brutal civil war, Cleopatra and Demetrius had at least three children, Seleucus, Antiochus and a daughter called Laodike.

[5] He was forced to retreat near Pelousion because his soldiers refused to obey him, and Cleopatra Thea, then in Antioch, rebelled against him and established her son Antiochus as king.

Cleopatra Thea fled the city, and probably went to Ptolemais, where she had married Alexander Balas some twenty years earlier.

[2][6] Cleopatra Thea thus procured an Egyptian alliance, causing Ptolemy to turn against Alexander II (whom he had previously supported as a means of keeping the Seleucids preoccupied with civil war).

By 123 BC Alexander II had been defeated and executed, Cleopatra and Grypus remaining joint rulers in Cilicia, Syria and Northern Mesopotamia.

114 BC, when Cleopatra Thea's other son, Antiochus IX, returned to Syria to claim the throne and civil war started again.