Xerxes is the central character of the Aeschylus play "The Persians." Xerxes is the protagonist of the opera Serse by the German-English Baroque Composer George Frideric Handel. It was first performed in the King's Theatre London on 15 April 1738. The famous aria "Ombra mai fù" opens the opera.

Xerxes (Ahasuerus) is portrayed by Richard Egan in the 1960 film Esther and the King and by Joel Smallbone in the 2013 film, The Book of Esther. In at least one of these films, the events of the Book of Esther are depicted as taking place upon Xerxes' return from Greece.

Later generations' fascination with ancient Sparta, particularly the Battle of Thermopylae, has led to Xerxes' portrayal in works of popular culture. He was played by David Farrar in the fictional film The 300 Spartans (1962), where he is portrayed as a cruel, power-crazed despot and an inept commander. He also features prominently in the graphic novel 300 by Frank Miller, as well as the film adaptation 300 (2007) and its sequel 300: Rise of an Empire (2014), as portrayed by Brazilian actor Rodrigo Santoro, in which he is represented as a giant man with androgynous qualities, who claims to be a god-king. This portrayal has attracted controversy, especially in Iran. Ken Davitian plays Xerxes in Meet the Spartans, a parody of the first 300 movie replete with sophomoric humour and deliberate anachronisms.

Gore Vidal, in his historical fiction novel Creation (1981), describes at length the rise of the Achemenids, especially Darius I, and presents the life and death circumstances of Xerxes. Vidal's version of the Persian Wars, which diverges from the orthodoxy of the Greek histories, is told through the invented character of Cyrus Spitama, a half-Greek, half-Persian, and grandson of the prophet Zoroaster. Thanks to his family connection, Cyrus is brought up in the Persian court after the murder of Zoroaster, becoming the boyhood friend of Xerxes, and later a diplomat who is sent to India, and later to Greece, and who is thereby able to gain privileged access to many leading historical figures of the period.

Other works dealing with the Persian Empire or the Biblical story of Esther have also referenced Xerxes, such as the video game Assassin's Creed II and the film One Night with the King (2006), in which Ahasuerus (Xerxes) was portrayed by British actor Luke Goss. He is the leader of the Persian Empire in the video game Civilization II and III (along with Scheherazade), although Civilization IV replaces him with Cyrus the Great and Darius I.

Almost immediately, Xerxes crushed revolts in Egypt and Babylon that had broken out the year before, and appointed his brother Achaemenes as satrap over Egypt. In 484 BC, he outraged the Babylonians by violently confiscating and melting down the golden statue of Bel (Marduk, Merodach), the hands of which the rightful king of Babylon had to clasp each New Year's Day. This sacrilege led the Babylonians to rebel in 484 BC and 482 BC, so that in contemporary Babylonian documents, Xerxes refused his father's title of King of Babylon, being named rather as King of Persia and Media, Great King, King of Kings (Shahanshah) and King of Nations (i.e., of the world). This comes from the Daiva Inscriptions of Xerxes, lines 6–13.