Hypsistarians, i.e. worshippers of the Hypsistos (Greek: Ὕψιστος, the "Most High" God), and similar variations of the term first appear in the writings of Gregory of Nazianzus (Orat. xviii, 5) and Gregory of Nyssa (Refutation of Eunomius' Confession 38), about AD 374. The term has been linked to a body of inscriptions that date from around 100 AD to around 400 AD, mostly small votive offerings, but also including altars and stelae, dedicated to Theos Hypsistos, or sometimes simply Hypsistos, mainly found in Asia Minor (Cappadocia, Bithynia and Pontus) and the Black Sea coasts that are today part of Russia.

Some modern scholars identify the group, or groups, with God-fearers mentioned in the Acts of the Apostles, non-Jewish (gentile) sympathizers with Second Temple Judaism.

A late 3rd century CE shrine in a wall of the ancient city of Oenoanda provides the strongest archaeological evidence for this cult. It is adorned with an inscription adapting a declaration of the Apollonian oracle in Didyma, describing the god as, "Self-begotten, un-taught, un-mothered, undisturbed, not permitting a name, many-named, dwelling in fire." Another inscription below the first dedicates a lantern to the Most High God. Another proof for the existence of the Hypsistarians is also found in the city of Oenoanda in the form of another epigraph close to the location of the shrine: the epigraph, dedicated by Chromatis, involves a vow to the Most High God and illustrates a practice of prayer at dawn, which aligns with the oracle's description and possibly suggesting a form of henotheistic worship practice.

More archaeological finds may be related to the presence of Hypsistarians. In what is now North Macedonia, the evidence for the presence of Hypsistarians includes three inscriptions from the Valley of the River Vardar, dated to the 2nd century AD. Here there are two altars with reliefs of eagles and a statuette of an eagle, which have not been previously connected to the cult but are considered indicative. Out of twenty-five inscriptions in the region, nineteen are devoted to Zeus Hypsistos (another name for the Hypsistarian God) and six to Theos Hypsistos, showing the local significance and development of the cult. In Phrygia, numerous small rural altars decorated with agricultural motifs, such as ears of wheat and grapes, indicate local worship practices. In the Bosporan Kingdom, several inscriptions and enrollment lists from Tanais and manumission inscriptions in Gorgippia and Panticapaeum demonstrate the existence of Jewish and syncretic pagan cults. In Athens, around 20 votive plaques and altars dedicated to Zeus Hypsistos found on the Pnyx hill highlight a healing cult associated with Hypsistos, with most dedications made by women. Throughout Anatolia, a great number of votive tablets and other inscriptions are evidence that referring to one or more gods as Most High (Hypsistos, often as Theos Hypsistos 'god most high', or as Zeus or Attis, but frequently unnamed) was widespread.

However, it is not certain that all of these inscriptions are actually related to the Hypsistarians. Indeed, calling a divinity "the highest" may just have been a form of emphasising how unique that divinity is, without excluding the possibility that other divinities are unique in their way, too.

The name Hypsistarioi first occurs in Gregory of Nazianzus (Orat., xviii, 5) and the name Hypsistianoi in Gregory of Nyssa (Contra Eunom., II), about 374 CE.

Gregory of Nazianzus describes a syncretic Jewish-pagan group that does not worship idols, reveres lamps and fire, and worships the Almighty (Pantokrator). They keep Sabbath and adhere to dietary restrictions, but they do not circumcise. Gregory of Nazianzus' description of this cult occurs in his eulogy for his father, who was a Hypsistarian before his conversion to Christianity:

Τῆς μὲν γὰρ τὰ εἴδωλα καὶ τὰς θυσίας ἀποπεμπόμενοι, τιμῶσι τὸ πῦρ καὶ τὰ λύχνα· τῆς δὲ τὸ Σάββατον αἰδούμενοι, καὶ τὴν περὶ τὰ βρώματα ἔστιν ἂ μικρολογίαν, τὴν περιτομὴν ἀτιμάζουσιν. Ὑψιστάριοι τοῖς ταπεινοῖς ὄνομα, καὶ ὁ Παντοκράτωρ δὴ μόνος αὐτοῖς σεβάσμιος.