As the elder sister of Theodosius II, she held much of the power when he came to the throne as a child in 408. She took a vow of virginity to avoid being forced into a marriage, and tended to rely on the support of the various Germanic military officers she appointed, such as the Alan Aspar. By 416 Theodosius was capable of ruling by himself, but she remained a very strong influence, having had herself proclaimed Empress in 414. That year she had Theodosius remove all pagans from the civil service; she was a devout Christian and under her influence both Theodosius and his wife Aelia Eudocia (a former pagan) became devout Christians as well. In 421 Theodosius declared war on Persia, due to Pulcheria's influence, apparently because the Persians were persecuting Christians. She did not oppose Arianism, the form of Christianity practised by the Germanic tribes. Theodosius originally supported Patriarch Nestorius, but Pulcheria, with the help of Archbishop Cyril of Alexandria, convinced him to return to Orthodoxy. Nestorius was exiled in 435. Pulcheria also convinced her brother to exile the Jews and destroy their synagogues in Constantinople.
In 441 Chrysaphius, a eunuch, convinced Theodosius to dismiss Pulcheria, although Chrysaphius simply took her place leaving Theodosius with little power. Pulcheria became a nun, but by 450, when Theodosius died, Pulcheria had been allowed to return to court. Chrysaphius and Pulcheria struggled for control after Theodosius' death; Pulcheria allied with the Germanic military officers, and married one of Aspar's generals, Marcian, declaring that Theodosius had declared Marcian his successor. The marriage was arranged with the understanding that he respect Pulcheria's vow of chastity. Pulcheria then had Marcian execute Chrysaphius.
In 451 she helped organize the Council of Chalcedon to condemn Nestorianism. The Council also condemned the Robber Synod of 449, which had supported the Monophysite heresy and the Monophysite abbot Eutyches, who was deposed and exiled at Chalcedon. At Chalcedon Pulcheria declared Flavian of Constantinople a martyr, after his deposition at the Robber Synod and his death at the hands of the supporters of Eutyches, whom he had opposed.
Pulcheria also commissioned many new churches in Constantinople, especially to the Virgin Mary. She died in July, 453, leaving Aspar as the dominant influence on Marcian, who himself died in 457. Pulcheria is recognized as a saint by the Roman Catholic Church and the Eastern Orthodox Church.