Orione was born into a poor family at Pontecurone, in the Province of Alessandria, in the Piedmont region of Italy, on the vigil of the feast day of the Nativity of St. John the Baptist.

In 1903 the group received the full authorization of the bishop as a religious congregation called the Sons of Divine Providence.

[2] One of the priests who was in his inner circle was Lorenzo Perosi, who later became Perpetual Director of the Sistine Chapel Choir and one of the most famous composers of sacred music.

He founded schools, farming colonies, charity organizations and nursing homes—always with a special emphasis on helping orphans and the poor.

In 1931, he founded the Shrine of the Madonna della Guardia in Tortona, which to this day is the principal church in the world for the Orionine order.

On March 8, 1940, on the eve of his departure for Sanremo, Don Orione is recorded as saying, "It is not among the palm trees that I would like to die," he said, "but amongst the poor who are Jesus Christ.

Orione's mortal remains have rested in the crypt of the Shrine of La Madonna della Guardia in Tortona, which he himself founded, since his burial on March 19, 1940.

In the United States, the national shrine and headquarters of the Sons of Divine Providence is located on a well-known hill in East Boston, Massachusetts, known as Orient Heights.