During the Intertestamental Period, significant events involving Artaxerxes I shaped the history of the Jewish people. Under the Persian Empire's control, which included the reign of Artaxerxes I, the Jews experienced various challenges. A notable incident during this time involved John, the son of Judas, son of Eliashib, who, driven by ambition for power, killed his brother Jesus (not Jesus Christ, but a figure named Jesus or Joshua in another language), a favorite of Bagoses, a general under Artaxerxes in command of the district. This fratricide, committed in the Temple in Jerusalem before the altar, intensified the guilt of the act and provoked a storm of rage across Judea, disrupting the fragile peace that had existed under earlier Persian rulers like Xerxes. This event marked a significant disturbance in the region, highlighting the internal conflicts and external pressures faced by the Jewish people under Persian governance during the era of Artaxerxes I.

The dating of biblical events holds significance for both history and prophecy. Several prophecies include long periods of time that must pass before their fulfillment, such as the Seventy Weeks Prophecy in Daniel 9:24-27, which spans nearly 500 years. These centuries require a firm date to anchor their commencement, as the angel Gabriel informs Daniel that the 70 weeks begin from the command to restore and build Jerusalem. The only command fitting these criteria was issued by Artaxerxes I in 457 BC, as recorded in Ezra 7:11-26.

Commissioned under God's direction by Artaxerxes I, who was very possibly the husband of Queen Esther, Ezra's priestly lineage is established. This man of faith began to move the entourage forward toward Jerusalem amidst a hostile world. After arriving, Ezra delivered the instructions to Artaxerxes I's deputies in the area, demonstrating his commitment to fulfilling the responsibilities entrusted to him under the king's authority.