Gregory Akindynos, a native of Prilep, had moved from Pelagonia to Thessaloniki and studied under Thomas Magistros and Gregory Bryennios.

He had become an admirer of Nikephoros Gregoras after he was shown an astronomical treatise of that scholar by his friend Balsamon in 1332, writing him a letter in which he calls him a "sea of wisdom".

From Thessaloniki, he had intended to move on to Mount Athos, but for reasons unknown, he was refused.

He has become involved in the theological dispute surrounding the doctrine of Uncreated Light between Gregory Palamas and Barlaam of Calabria.

A student of Palamas', he has mediated between the two from 1337, warning Barlaam in 1340 that his attempts against his doctrine would be futile.

The dispute over Hesychasm (the Eastern Orthodox Church's mystical teaching on prayer) comes before a synod held at Constantinople in May 1341 and presided over by the emperor Andronikos III Palaiologos.

The assembly, influenced by the veneration in which the writings of Pseudo-Dionysius are held in the Eastern Church, condemns Barlaam, who recants.

Emperor Andronikos III, Barlaam's primary supporter, had died just five days after the synod ended.

Although Barlaam had initially hoped for a second chance to present his case against Palamas, he soon realizes the futility of pursuing his cause, and leaves for Calabria where he converts to the Roman Church and is appointed Bishop of Gerace.

After Barlaam's departure, Gregory Akindynos becomes the chief critic of Palamas’ position, denouncing it as Messalianism, A second council held in Constantinople in August 1341 condemns Akindynos and affirms to findings of the earlier council, issuing a doctrinal definition on grace and taking a stand in reference to Western teachings.

Akindynos and his supporters gain a brief victory at the third synod held on November 4, 1344, which excommunicates Palamas and one of his disciples, Isidore Buchiras.

Palamas and Buchiras recant.