The Shrine of Our Lady of Guisborough has been a focus of devotion throughout the centuries.
Nobles gave gifts of land, money and goods and were buried as close as possible to the High Altar of Our Lady.
The Guild of Our Lady of Guisborough maintained a priest to celebrate the daily Lady Mass. They had three guild houses in the town.

The most famous pilgrim to visit the Shrine was St Malachy of Armagh. St Bernard of Clairvaulx describes how on one of his visits to Guisborough he cured a girl of cancer. Malachy was the first officially canonised Irish Saint. The book foretelling future popes, "the Prophecies of St Malachy" is attributed to him. St Malachy visited Guisborough more than once.

The clearest reference to the Shrine as a place of pilgrimage is found in the will of William Ecopp, Rector of Helerton, dated 6 September, 1472. He asks that pilgrims be sent on his behalf to the following shrines of Our Lady, Walsingham, Lincoln, Doncaster, Scarborough, Guisborough, Jesmond and Carlisle, and that an offering be made at each.