Following the death of their mother (175 BC), she was married to her brother in 173 BC, Ptolemy VI. They and their brother, Ptolemy VIII, were co-rulers of Egypt from 171 BC to 164 BC.
In 170 BC, Antiochus IV of Syria invaded Egypt, resulting in a war which Egypt eventually won with Rome's help in 168 BC.
She became regent for her son Ptolemy VII on her husband's death in 145 BC, and married her other brother, Ptolemy VIII Euergetes II "Physcon" the next year, whereupon Physcon slew his nephew/stepson and made himself king. In 142 BC he took her younger daughter, his niece, Cleopatra III, as wife without divorcing his sister and made his new wife joint ruler.
Cleopatra II led a rebellion against Physcon in 131 BC, and successfully drove him and Cleopatra III out of Egypt. She then proclaimed Physcon's twelve-year-old son, Ptolemy Memphitis, as King, and herself as coregent (though she technically was the sole ruler at this point). However, Physcon managed to have Memphitis killed and sent the pieces of his body to Cleopatra, and she remained sole ruler of Egypt. She offered the throne to Demetrius II of Syria, but he was assassinated by Physcon, and Cleopatra left for Syria in 127 BC. Physcon then returned to Egypt and reclaimed the throne. A public reconciliation of Cleopatra and Physcon was declared in 124 BC. After this she ruled jointly with her brother and daughter until 116 BC when Ptolemy died, leaving the kingdom to Cleopatra III. She herself died shortly after.
