Agathias was a native of Myrina (Mysia). His father was Memnonius. His mother was presumably Pericleia. A brother of Agathias is mentioned in primary sources, but his name has not survived. Their probable sister Eugenia is known by name. The Suda clarifies that Agathias was active in the reign of the Roman emperor Justinian I, mentioning him as a contemporary of Paul the Silentiary, Macedonius of Thessalonica and Tribonian.
Agathias mentions being present in Alexandria as a law student at the time when an earthquake destroyed Berytus (Beirut). The law school of Berytus had been recognized as one of the three official law schools of the empire (533). Within a few years, as the result of the disastrous earthquake of 551, the students were transferred to Sidon. The dating of the event to 551: as a law student, Agathias could be in his early twenties, which would place his birth to c. 530.
He mentions leaving Alexandria for Constantinople shortly following the earthquake. Agathias visited the island of Cos, where "he witnessed the devastation caused by the earthquake". At the fourth year of his legal studies, Agathias and fellow students Aemilianus, John and Rufinus are mentioned making a joint offering to Michael the Archangel at Sosthenium, where they prayed for a "prosperous future".
He returned to Constantinople in 554 to finish his training, and practised as an advocatus(scholasticus) in the courts. John of Epiphania reports that Agathias practiced his profession in the capital. Evagrius Scholasticus and Nikephoros Kallistos Xanthopoulos describe Agathias as a rhetor ("public speaker"). The Suda and a passage of John of Nikiû call him "Agathias the scholastic". He is known to have served as pater civitatis ("Father of the City", effectively a magistrate) of Smyrna. He is credited with constructing public latrines for the city. While Agathias mentions these buildings, he fails to mention his own role in constructing them.
Literature, however, was his favorite pursuit, and Agathias remains best known as a poet. Of his Daphniaca, a collection of short poems in hexameter on 'love and romance' in nine books, only the introduction has survived. But he also composed over a hundred epigrams, which he published together with epigrams by friends and contemporaries in a Cycle of New Epigrams or Cycle of Agathias, probably early in the reign of emperor Justin II (r. 565–578). This work largely survives in the Greek Anthology—the edition by Maximus Planudes preserves examples not found elsewhere. Agathias's poems exhibit considerable taste and elegance.
He also wrote marginal notes on the Description of Greece (Ἑλλάδος περιήγησις) of Pausanias.
Almost equally valued are Agathias's Histories, which he started in the reign of Justin II. He explains his own motivation in writing it, as simply being unwilling to let "the momentous events of his own times" go unrecorded. He credits his friends with encouraging him to start this endeavor, particularly one Eutychianus. This work in five books, On the Reign of Justinian, continues the history of Procopius, whose style it imitates, and is the chief authority for the period 552–558. It deals chiefly with the struggles of the Imperial army, under the command of general Narses, against the Goths, Vandals, Franks and Persians.
The work survives, but seems incomplete. Passages of his history indicate that Agathias had planned to cover both the final years of Justin II and the fall of the Huns but the work in its known form includes neither. Menander Protector implies that Agathias died before having a chance to complete his history. The latest event mentioned in the Histories is the death of the Persian king Khosrau I (r. 531–579); which indicates that Agathias was still alive in the reign of Tiberius II Constantine (r. 578–582). The emperor Maurice (r. 582–602) is never mentioned, suggesting that Agathias was dead by 582.
Menander Protector continued the history of Agathias, covering the period from 558 to 582. Evagrius Scholasticus alludes to Agathias' work, but he doesn't seem to have had access to the full History.
Myrina is known to have erected statues to honor Agathias, his father Memnonius, and Agathias' unnamed brother. He seems to have been known to his contemporaries more as an advocatus and a poet. There are few mentions of Agathias as a historian.
Few details survive of his personal life – mainly in his extant poems. One of them tells the story of his pet cat eating his partridge. Another mentions him visiting Ephyra (now Kichyro), in Epiros in Greece. No full account of his life survives.