Artaxerxes was the eldest son of Darius II and Parysatis. Ancient writers preserve Arsaces and Arsicas as forms of his earlier name, while Artaxerxes was the royal name under which he ruled. Plutarch explains that he was born before his father became king, whereas his younger brother Cyrus was born after Darius's accession. In that account, Parysatis favoured Cyrus and argued that the circumstances of his birth strengthened his claim to succeed. Darius nevertheless chose the elder son. This family dispute is part of the Greek literary account of the succession, not evidence that a single uncontested Persian rule required preference for a child born during his father's reign. When Darius died, Artaxerxes took the throne. His precise birth year is uncertain, and the conflicting ages and regnal totals in later writers should not be combined into a falsely exact biography.

Plutarch describes an accusation against Cyrus at the new king's inauguration at Pasargadae. The ceremony involved a sanctuary of a warlike goddess whom Plutarch compares with Athena; the passage does not simply identify her by the name Anahita. The new ruler was said to put on garments associated with Cyrus the Great as part of the ritual. Tissaphernes and a priest accused Cyrus the Younger of planning to attack his brother during the ceremony. Plutarch preserves disagreement over whether the charge was false or whether Cyrus had actually been discovered waiting to carry it out. Parysatis intervened when her son faced execution, and Cyrus was released and returned to his position in the western empire. The episode sets up the later rebellion in the literary narrative, but the accusation and the alleged attempted assassination should not be treated as equally certain facts.

Cyrus assembled forces in the western provinces, including a substantial body of Greek mercenaries, and marched against Artaxerxes in 401 BCE. The armies met at Cunaxa near Babylon. Cyrus was killed, and the king retained the throne. Ancient accounts disagree over details of the encounter, including who inflicted particular wounds and who killed Cyrus. In the version of Ctesias reported by Plutarch, Artaxerxes received a wound in the chest and was treated by the physician; the knee wound in Plutarch's battle narrative belongs to Cyrus, not to Artaxerxes. Cyrus's head and right hand were cut off after his death. His Greek troops, however, had not simply surrendered with the collapse of their employer's claim. Their subsequent negotiations, the loss of commanders and the long retreat became the subject of Xenophon's Anabasis. Xenophon was one of the leaders in that retreat, rather than the sole commander of every stage. The episode connects a Persian dynastic conflict with an unusually detailed Greek account of campaigning within the empire.

Ctesias was already associated with the Persian court before Cunaxa; treating the king's wound was not the event that first brought him there. His position gave him material for the Persica, a history in twenty-three books, and for the Indica, a work describing India and its reported wonders. Neither survives intact. Much of what can be read today comes through excerpts, summaries and quotations by later authors, including Photius and Plutarch. Their transmission requires care, especially where Ctesias's account differs from another writer's. The manticore belongs to this literature of distant wonders: a creature described with features of a lion, a human face and a dangerous tail. Aelian reports Ctesias's claim that such a creature had been brought to a Persian king, but that passage does not name Artaxerxes II. The report is evidence for an ancient story about an extraordinary animal, not proof that such an animal existed or that Artaxerxes personally received it. Ctesias's importance here is as a channel through which Persian court experience and accounts of distant lands entered Greek literature.

The conflict between Parysatis and Stateira is among the best-known stories in Plutarch's biography. He presents the king's mother and wife as rivals and describes precautions taken when they ate together. He then reports an account in which a shared bird was divided using a knife poisoned on one face, allowing one portion to be served to Stateira while the other remained harmless. Plutarch explicitly distinguishes the versions of Ctesias and Deinon, including disagreement over who handled the serving. The account should therefore not be simplified into a single witnessed sequence involving two knives and an undisputed servant. Gigis, a confidante of Parysatis, was implicated and executed in the narrative. Parysatis went to Babylon, which Plutarch describes as a departure she requested, and was later recalled. Stateira's death and the accusations surrounding it survive through these hostile and dramatic court accounts; claims about the king's unspoken feelings or the one person he truly trusted go beyond what can be established from them.

Artaxerxes's reign lasted approximately forty-six years and included both challenges to imperial authority and significant interventions in Greek affairs. The settlement commonly called the King's Peace, agreed in 387/386 BCE, asserted the Persian king's claim over the Greek cities of Asia while setting terms for relations among Greek states. The reign also saw an unsuccessful attempt to recover Egypt and revolts among provincial rulers. These events should be described individually rather than treated as automatic proof of an empire moving in a single direction. Royal evidence offers another perspective: an inscription from Susa names Artaxerxes's ancestry, invokes Ahuramazda, Anahita and Mithra, and records the restoration of a palace hall. Such texts do not remove the need to examine the Greek accounts, but they show the king presenting his own dynastic and religious authority. He died around 358 BCE and was succeeded by his son Ochus, who ruled as Artaxerxes III. His historical reign and his portrayal in later literature remain connected but distinct subjects.