He became bishop of the town of Nyssa in 372. While Nyssa itself was not a terribly large or important town, his brother Basil wanted him to be close to the latter's see in Caesarea. He was present at the Council of Antioch, and later at the Second Ecumenical Council which took place in Constantinople. There he was a defender of the Nicene Creed against the Arians.
Gregory is remembered above all for two major contributions to theology. The first is his doctrine of the Trinity, a development of the theology of Basil and their mutual friend Gregory Nazianzus. Following Basil's lead, Gregory argues that the three Persons of the Trinity can be understood along the model of three members of a single class: thus, the Father, Son, and Holy Spirit are three in the same way that Peter, Paul, and Timothy are three men. So why do we not say there are three Gods? Gregory answers that, normally, we can distinguish between different members of the same class by the fact that they have different shapes, sizes, and colours. Even if they are identical, they still occupy different points in space. But none of this is true of incorporeal things like God. Even lesser spiritual beings can still be distinguished by their varying degrees of goodness, but this does not apply to God either. In fact, the only way to tell the three Persons apart is by their mutual relations - thus, the only difference between the Father and the Son is that the former is the Father of the latter, and the latter is the Son of the former. As Gregory puts it, it is impossible to think of one member of the Trinity without thinking of the others two: they are like a chain of three links, pulling each other along. Gregory's ideas here would be very influential on the Trinitarian theology of Augustine of Hippo.
Gregory's second main contribution is his spiritual theology. He is the first Christian theologian to argue for the infinity of God. Origen, a major influence on Gregory, had explicitly argued that God is limited, an essential notion in Platonism, since to be limited is to be clearly defined and knowable. Gregory, however, argues that if God is limited he must be limited by something greater than himself; he is therefore without boundaries. The idea had already been developed by some Platonic philosophers, especially Plotinus, another important influence on Gregory, but he is the first Christian to defend it, apart from some hints in the work of Irenaeus.
Accordingly, Gregory argues that since God is infinite he cannot be known. Origen had spoken of the spiritual journey as a progression of increasing illumination, as the mystic studies Scripture and comes to learn more about God. Gregory, however, calls it a darkening. Like earlier authors, including Philo, he uses the story of Moses as an allegory for the spiritual life. Moses first meets God in the burning bush, a theophany of light and illumination, but then he meets him again in the cloud, where he realises that God cannot be seen by the eyes. Ascending Mount Sinai, he finally comes to the "divine darkness", and realises that God cannot be known by the mind either. It is only through not-knowing and not-seeing that God can, paradoxically, be known and seen. This notion would be extremely influential in both Western and Eastern spirituality, via the writings of Pseudo-Dionysius the Areopagite.
Related to this is Gregory's idea of epiktasis or constant progress. The Platonic philosophy was that stability is perfection and change is for the worse. In contrast, Gregory described the ideal of human perfection as constant progress in virtue and godliness. In his theology, God himself has always been perfect and has never changed, and never will. Humanity fell from grace in the Garden of Eden, but rather than return to an unchanging state, humanity's goal is to become more and more perfect, more like God, even though humanity will never understand, much less attain, God's transcendence. This idea has had a profound influence on the Eastern Orthodox teaching regarding theosis or "divinization".
Gregory's Trinitarian doctrine can be found in his Why there are not three Gods and a letter to Basil which has been erroneously classified as Basil's 38th letter. His spiritual writings include Life of Moses and 15 homilies On the Song of Songs. A large number of letters, sermons, philosophical works and short essays on a number of topics also survive.