Pixodarus was the youngest son of Hecatomnus, who had obtained the satrapy of Caria in 392/391. He had been succeeded by his oldest son Maussolus, his oldest daughter Artemisia, and his second son Idrieus. When the latter died in 344, he left the satrapy, which now also included possessions outside the Achaemenid Empire to Ada, the second daughter of Hecatomnus. Although this was confirmed by the Persian king Artaxerxes III Ochus, Pixodarus did not appreciate this arrangement. In 340, he expelled Ada from her capital Halicarnassus (modern Bodrum) and became satrap. It is hard to see how he could have done this without external help, and perhaps the supreme commander of the Persian forces in Asia Minor, Mentor of Rhodes, was somehow involved.
Pixodarus was not a newcomer to the political game. A fragment of the Athenian comic poet Epigenes suggests that as a very young man, Hecatomnus had sent him on an embassy to Athens. This must have happened before the death of Pixodarus' father in 377. For the next 37 years, we hear nothing about Pixodarus.
Although Pixodarus had seized the throne, Ada still received support from the countryside and kept possession of the fortress of Alinda. This created problems when the Macedonian commander Parmenion invaded Asia in the spring of 336: although the Persians needed all available troops to push back the intruder, Pixodarus could not leave Caria.
However, Pixodarus had already attempted diplomatic moves to ally himself to Macedonia. In 337, he had offered the hand of a daughter to a Macedonian prince, Arridaeus, and king Philip liked the idea. His crown prince Alexander, however, thought he was forgotten, sent a private embassy to Halicarnassus, asking for the hand of the princess. Philip was angry, punished his son, and the Macedonian-Carian alliance was canceled.
In the autumn of 336, Alexander succeeded his father, and in the spring of 334, he joined Parmenion, defeated the Persians at the Granicus and marched to the south, where Sardes and Miletus were captured. At more or less the same time, Pixodarus died.
He was succeeded by his son-in-law Orontobates, a Persian, who appears to have married the girl who was once supposed to have married Arridaeus. The date of this wedding is unknown, but it is likely that it was celebrated before 334. If Pixodarus had died without son-in-law, the Achaemenid king Darius III Codomannus could simply have recognized Ada, and would have created a strong Caria; the fact that he did not, suggests that Orontobates had already become a member of the dynasty and had a claim to the office.
When Alexander proceeded to Caria, he allied himself to Ada, received the surrender of Alinda, captured Halicarnassus, and reappointed Ada as satrap. Orontobates' is unknown.