Anastasia entered historical record when her husband Constantine IV succeeded to the throne in 668. On September 15, 668, her father-in-law Constans II was assassinated in his bath by his chamberlain. He resided for the last few years of his reign in Syracuse, while Constantine and Theodora remained in Constantinople.

Anastasia became the senior Empress consort when news of the assassination reached the court. The birth of her first son, Justinian II, can be estimated to 668/669 due to the chronologies of Theophanes the Confessor and Ecumenical Patriarch Nikephoros I of Constantinople. A reference in De Administrando Imperio by Constantine VII, places the birth in Cyprus.

Her only other son mentioned is named as Heraclius in the Liber Pontificalis. The entry on Pope Benedict II (term 26 June 684 – 8 May 685), mentions the Pope receiving locks of hair from both Justinian and Heraclius, presumably as a gesture of goodwill by their father.

Constantine IV died of dysentery in September, 685. Anastasia is known to have survived him by more than two decades.

Justinian succeeded to the throne and would go on to earn a reputation for excessive harshness. Justinian needed funds for his building projects and allowed Stephen the Persian, his logothetes tou genikou (responsible for the taxation of the state), to secure them by any means. Both Theophanes and Nikephoros claimed that Stephen inflicted corporal punishment or plain torture while trying to collect the needed funds.

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