Manuel 6 was a native of Armenia; he was paternal uncle of the empress Theodora 2 (and was therefore the brother of Marinos 10); at the beginning of the reign of Michael II (Michael 10), in 842, he held the title of magistros; at an earlier stage of his career (cf. below) he held office as strategos of the Armeniakoi; he was one of three advisers left by the late emperor Theophilos 5 to oversee public affairs during the minority of Michael III (Michael 11) (see Theoktistos 3 and Bardas 5): Theoph. Cont. IV 1 (p. 148) (Μανουὴλ ὁ μάγιστρος ἐκ τῶν Ἀρμενίων καταγόμενος, ὅς καὶ θεῖος ἀπὸ πατρὸς τῆς δεσποίνης ὑπῆρχεν), Zon. XVI 1. 1 (τὸν μάγιστρον Μανουὴλ), 2. 23 (τῷ μαγίστρῳ Μανουὴλ). In a late source (Zonaras) he is said to have been at first reluctant to see the veneration of icons restored: Zon. XVI 1. 3. He is said to have fallen gravely ill but been promised by monks from the Stoudios monastery and by others from the East whom he had met when strategos there (ὅτε τῶν Ἀρμενιακῶν ἐστρατήγει) that he would regain his health if he undertook to secure the restoration of icon veneration; he recovered and persuaded first his two fellow advisers and then the empress Theodora 2 that it was time to change the policy on icons: Theoph. Cont. IV 1-2 (pp. 148-150), Zon. XVI 1. 4-8. It was this man (ὁ μάγιστρος Μανουὴλ) who extracted the truth from a woman (Anonyma 21) who made allegations of immoral conduct against the patriarch Methodios 1; he threatened her with death and then when she admitted the deceit he sent men to her residence where evidence was found that she had been bribed: Theoph. Cont. IV 10 (pp. 159-160), Zon. XVI 1. 26, 33. As one of the imperial advisers he normally lived in the palace; however dissension between him and Theoktistos 3 and a whispering campaign led to allegations involving high treason, and Manuel 6 chose to free himself from them by leaving the palace and going to live in his own house, which was situated close to the reservoir of Aspar; from there he went each day to the palace to take part in public business; he later converted his house into a monastery (εἰς σεμνείου τύπον) and was in due course buried there: Theoph. Cont. IV 18 (p. 168), Scyl., p. 94, Zon. XVI 2. 23 (his departure from the palace). After the murder of Theoktistos 3 he was inspired to deliver warning verses to Bardas 5: Theoph. Cont. IV 19 (pp. 170-171), Scyl., p. 95. He supposedly fought in battle with the emperor Michael 11 against an Arab army led by Amr 2 in c. 857, when the emperor sought to avenge his defeat at Samosata the year before; during the battle Michael 11 fled to a hill called Anzen and was in danger of capture by the Arabs until Manuel 6 came to his rescue and with difficulty brought him to safety: Theoph. Cont. IV 24 (pp. 177-179), Zon. XVI 3. 16-18. This story is clearly a doublet of that told about the emperor Theophilos 5 and Manuel 1 and in spite of the circumstantial details of place names and the name of the Arab leader (Amr 2) should be regarded as fiction and of no historical value. He died of illness some time before the death of Petronas 5 (therefore before 865): Theoph. Cont. IV 25 (p. 184), Zon. XVI 3. 29 (ἤδη γὰρ ὁ μάγιστρος Μανουὴλ ἀπεβίω). Probably identical with Manuel, patrikios, basilikos protospatharios, magistros and bagylos of the emperor, who owned a seal dateable to the mid ninth century: Zacos and Veglery 2151A. The name and titles read: Μανουὴλ πατρικίῳ, βασιλικῷ πρωτοσπαθαρίῳ μαγίστρῳ καὶ βαγύλῳ τοῦ δεσπότου. The latter title presumably alludes to his role as guardian (and perhaps tutor) of Michael III (Michael 11).

His story is also told in Genesius. Protomagistros (Μανουὴλ ὁ πρωτομάγιστρος); he and Theoktistos 3 were the advisers to the emperor Michael III (Michael 11) and his mother Theodora 2; at Michael 11's accession he addressed the troops assembled in the hippodrome and secured their promise of loyalty to the new emperor; the troops allegedly thought at first that he was seeking the throne himself: Genesius IV 1. He fell gravely ill and was told by the Stoudite monks attending him that he would not recover unless he undertook to end the ban on icon veneration; he did recover, unexpectedly, and began to urge the empress Theodora 2 to restore the veneration of icons: Genesius IV 2. He was one of the delegation of high ranking senators who visited the patriarch Methodios 1 to question him about allegations that he was the father of a son, Metrophanes 1; called the protomagistros (ὁ πρῶτα φέρων Μανουὴλ ἐν μαγίστροις); after hearing Methodios 1's statement proving his innocence, Manuel 6 questioned the woman who had made the allegation and by using threats secured a confession and information about those responsible and about the amount she had been paid: Genesius IV 5. The empire is said to have been well managed under Michael 11 and Theodora 2, thanks to the advice of Manuel 6 and Theoktistos 3 (μεσιτευόντων τῶν προδηλωθέντων ἀνδρῶν): Genesius IV 7. They lived together in the imperial palace and conducted public affairs in harmony, until Theoktistos 3 turned against Manuel 6 and secretly accused him of treachery; when Manuel 6 learned of this he left the palace and commuted there from his own home, which was near the Cistern of Aspar, to deal with public business; he lived to a great age and converted his house (τὸν ἑαυτοῦ οἶκον) into a monastery, where he was buried: Genesius IV 8. After the murder of Theoktistos 3 by Bardas 5, Manuel 6 allegedly delivered a cryptic warning that Bardas 5 had thereby sealed his own fate: Genesius IV 10. He is said to have saved the life of the emperor Michael 11 when the Roman forces were trapped on Mt Anzes by the Arabs under Amer (Amr 2) (see above); he is styled μάγιστρος: Genesius IV 14. See also under Manuel 1.

At the start of the reign of the emperor Michael 11 when the empress Theodora 2 administered the government Manuel 6 was "captain of the host" and commander of the whole army: Bar Hebr., p. 140.

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