He was the son of Eumenes II and wife Stratonike and the nephew of Attalus II, whom he succeeded. Married to Berenice (?) (in Greek Βερενίκη), they were the parents of a daughter, Princess of Pergamum (it is assumed that this link is a daughter since Attalus III is noted as dying without leaving heirs), who was the mother of Berenice (?), married to Deiotaros I Philoromaios, King of Galatia. "Philometor Euergetes" means "Loving-his-Mother, Benefactor" in Greek. He was so-called because of his close relationship with his mother Stratonice.
Attalus III had little interest in ruling Pergamon, devoting his time to studying medicine, botany, gardening, and other pursuits. He had no male children or heirs of his own, and in his will he left the kingdom to the Roman Republic. Tiberius Gracchus requested that the treasury of Pergamon be opened up to the Roman public, but the Senate refused this.
Not everyone in Pergamon accepted Rome's rule. Aristonicus, who claimed to be Attalus' brother as well as the son of Eumenes II, an earlier king, led a revolt among the lower classes with the help of Blossius. The revolt was put down in 129 BC, and Pergamon was divided among Rome, Pontus, and Cappadocia.