Pope St. Caius reigned for 13 years, from 283 to his death in 296 soon before the Diocletian persecution. He was related to Emperor Diocletian, who was responsible for one of the last major Christian persecutions during the early Church era. Caius made it mandatory for a man to serve as a priest before being appointed as a bishop early in his pontificate.

He is believed to have been driven into hiding in the catacombs for eight years before dying a confessor, although the source from which this information is derived is regarded as untrustworthy by most historians.

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