He came under the influence early of the bishop Theodore, was baptized by him, and succeeded, after much opposition, in bringing his father and mother to Christianity.

He embraced the clerical state, and rapidly rose to the position of archdeacon, when his virtues and notable powers as a preacher made him known to Saint Ambrose, at whose instance Pope Damasus I (r. 366–386) called him to Rome, and employed him in various important missions, including a legation to Constantinople.

There are grounds for believing that he actually died in 417, on 25 May, on which day the ancient tower where he is supposed to have lived, near the Ponte Vecchio, was annually decorated with flowers.

There was also a glass-paste mosaic panel The Bust of Saint Zenobius by the 16th century miniaturist Monte di Giovanni, but it is now on display in the Museo dell'Opera del Duomo.

According to tradition, during the 9th-century translation of Saint Zenobius's remains from the Basilica of San Lorenzo to the then-Cathedral of Santa Reparata, the bier carrying his body touched a dead elm tree near the Baptistery, causing it to miraculously burst into bloom despite it being winter.

It is also said that after his death, a dead elm burst into life after his body touched it while being borne to the cathedral for burial.

Zenobius is often depicted with a dead child or man in his arms, or a flowering elm, both in reference to his miracles.