Athenodorus was born in Canana, near Tarsus (in modern-day Turkey); his father was Sandon. He was a student of Posidonius of Rhodes, and the teacher of Octavian (the future Caesar Augustus) at Apollonia.
In 44 BC, he seems to have followed Octavian to Rome and continued mentoring him there. He is reputed there to have openly rebuked the Emperor, and to have instructed him to recite the alphabet before reacting in anger. Later, Athenodorus returned to Tarsus, where he was instrumental in expelling the government of Boëthus and drafting a new constitution for the city, the result of which was a pro-Roman oligarchy.
Athenodorus is also written of by Pliny the Younger, who tells us of Athenodorus' renting of a haunted house in Athens. Athenodorus was wary because the house was exceptionally cheap for its size. When Athenodorus was writing a book of philosophy, late at night, a ghost is said to have come to him. The ghost, who was bound with chains, beckoned Athenodorus to follow him, leading him to a courtyard, where the ghost suddenly vanished. Athenodorus marked the spot, and the next day, with the permission of the city magistrates, he dug up the earth from that spot, where he found the skeleton of an old man, bound with chains. After the skeleton was given a proper burial, the ghost was said to have never haunted that house again.
- A work against the Categories of Aristotle (although this is sometimes credited to Athenodoros Cordylion).
- A history of Tarsus.
- A work of some kind dedicated to Octavia Minor.
- A work entitled περί σπουδη̃ς και παιδείας ("On zeal and youth").
- A work entitled περίπατοι ("Discourses").
None of these are extant, but he also assisted Cicero in writing his De Officiis and it has been suggested that his work may have influenced Seneca and Saint Paul. Following his death, an annual festival and sacrifice was held in Tarsus in his honour.
- Strabo, xiv. 14
- Pliny the Younger (1909–14). "LXXXIII. To Sura". In Charles W. Eliot. Letters, by Pliny the Younger; translated by William Melmoth; revised by F. C. T. Bosanquet.. The Harvard Classics 9. New York: P.F. Collier & Son.
- Plutarch: Life of Publicola 17.