Arsinoe's paternal grandfather was Agathocles of Pella, a nobleman who was a contemporary to King Philip II of Macedon who reigned 359-336 BC, while her maternal grandfather was the powerful Regent Antipater. Arsinoe I was named in honor of an unnamed grandmother, who may have been the mother of Lysimachus or the mother of Nicaea whose both names of these women are unknown. Little is known of her life prior to her marriage.
Between 289/88 and 281 BC, Arsinoe became the first wife of Ptolemy II Philadelphus, pharaoh of the Ptolemaic Kingdom, who was also her distant maternal cousin. Arsinoe I married Ptolemy II as part of an alliance between her father and Ptolemy II, against Seleucus I Nicator.
Arsinoe was, by marriage, Queen of the Ptolemaic Kingdom. Arsinoe bore Ptolemy II three children; two sons: Ptolemy III Euergetes, Lysimachus of Egypt and a daughter called Berenice. At an unknown date between after 279-274/3 BC, the sister of Ptolemy II, who is known as Arsinoe II, arrived in Egypt. She was the last wife of Lysimachus and had fled from her half-brother and husband Ptolemy Keraunos. Probably at the instigation of Arsinoe II, charges of conspiring to assassinate Ptolemy II were soon brought against Arsinoe.
As a result of the charges, Ptolemy II convicted Arsinoe of plotting against him. He repudiated her then exiled her to Coptos in Upper Egypt. It is chronologically plausible that these events were also connected to the banishment of Ptolemy II's niece Theoxena, as Theoxena was sent to the Thebaid, perhaps to Coptos as well.
Afterwards, Ptolemy II married his sister, Arsinoe II, and after her death, his children with Arsinoe were officially regarded as the children of Arsinoe II.
Arsinoe I lived in exile for twenty years. During her exile, she lived in great splendour and enjoyed considerable privilege, since she was the former wife of a pharaoh. Her first son with Ptolemy II succeeded his father after his death.
A surviving stele has been found at Coptos which refers to Arsinoe I. The Stele is of Senu-sher, a steward of Arsinoe I and the Stele is assigned to Arsinoe I's exile. The stele calls Arsinoe I the "king’s wife", but her name is not enclosed in the royal cartouche as was customary for an Egyptian queen. Another piece of surviving evidence connected to Arsinoe I is a Phoenician inscription found at Lapithos, Cyprus, which is dated in the 11th or 12th year in the reign of Ptolemy II. The inscription refers to a sacrifice instituted by Yatonba’al on behalf of "the legitimate scion and his wife", hence refers to Arsinoe I. As Arsinoe I was disgraced as a traitor, the fact the person who did the sacrifice on her behalf strongly suggests that the news of her disgrace had not yet reached him.