When Aristobulus I died after just one year on the throne, his widow Salome Alexandra did something audacious. She released Aristobulus's brothers from prison, where he had kept them in chains, and placed the crown on the head of Alexander Jannaeus, the eldest survivor. Josephus records a strange detail: Jannaeus had been hated by his father John Hyrcanus from birth and was never even permitted to appear in his presence. The reason, according to Josephus, was that God had appeared to Hyrcanus in a dream and revealed that Alexander would be his successor, and this grieved the old king, who preferred his other sons.

Alexander Jannaeus inherited the throne and immediately began expanding Hasmonean territory. He besieged Ptolemais on the Mediterranean coast, but his ambitions drew the attention of Ptolemy Lathyrus, the exiled king of Egypt who now ruled Cyprus. Ptolemy landed with a large army, and the two sides met at the Jordan River. The battle was devastating. Ptolemy's forces slaughtered 30,000 Jewish soldiers, then swept through Judean villages committing atrocities, dismembering women and children and boiling their body parts in cauldrons. Josephus writes that this was done deliberately to spread terror.

Alexander was saved only because Ptolemy's own mother, Cleopatra III, sent an Egyptian army to drive her son out of the region. She had no love for her exiled son, and she had no intention of letting him build a new empire in Syria. One of her generals, a Jew named Ananias, warned her against betraying Alexander, arguing that turning on a Jewish ally would make her an enemy of the entire Jewish people. Cleopatra listened and instead made an alliance with Jannaeus.

With his southern border secure, Alexander turned east and north, conquering cities across the Golan and Transjordan. But his own people turned against him. During the festival of Sukkot, the crowd pelted him with citrons and accused him of being unfit for the priesthood, claiming his mother had been a war captive. Alexander responded with massacres. He hired foreign mercenaries to slaughter six thousand of his own citizens at the festival.

This atrocity ignited a full-scale civil war that lasted six years. The Pharisees led a popular uprising against the king, and the fighting killed 50,000 Jews on both sides. When the rebels grew desperate, they committed the ultimate betrayal: they invited Demetrius III, a Seleucid prince, to invade Judea and help them overthrow their own king. Demetrius defeated Alexander in battle, but then 6,000 Jewish rebels switched sides, unable to stomach fighting alongside a foreign conqueror against a Jewish king. Demetrius withdrew, and Alexander had his revenge.