Zenobia's husband, Odaenathus (Odaenathus, Septimius), Rome's client ruler of Palmyra, had by 267 recovered the Roman East from Persian conquerors. After Odaenathus and his eldest son (by his former wife), Herodes (or Herodianus), were assassinated in 267 or 268, Zenobia became regent for her own young son Wahballat (called Vaballathus in Latin, Athenodorus in Greek). Styling herself queen of Palmyra, she had Vaballathus adopt his father's titles of “king of kings” and corrector totius Orientis (“governor of all the East”).

Nevertheless, unlike Odaenathus, Zenobia was not content to remain a Roman client. In 269 she seized Egypt, then conquered much of Asia Minor and declared her independence from Rome. Marching east, Aurelian defeated her armies at Antioch (now Antakya, Turkey) and at Emesa (now Ḥimṣ, Syria) and besieged Palmyra. Zenobia and Vaballathus tried to flee from the city, but they were captured and taken to Rome (272). The Palmyrenes soon surrendered. When they revolted again in 273, the Romans recaptured and destroyed the city. Zenobia and two of her sons, Herennianus and Timolaus, graced the triumphal procession that Aurelian celebrated at Rome in 274. Vaballathus's fate is unknown, but Zenobia married a Roman senator and presumably spent the rest of her life at his villa near Tibur (now Tivoli, Italy).