The first Mayor of Hull was Sir William De La Pole, who also held the manor of Myton. He decided to build a monastery on his land (in Myton - later Sculcoates) but died before he was able to do so.  It was left to his son, Sir Michael De La Pole (1st Earl of Suffolk) to carry out his wishes. The Priory he built possibly replaced another religious foundation on the same site. In 1378 he invited the monks of the Carthusian Order to live there. It was usually called the Carthusian Priory of Hull due to its close proximity to the town. As the headquarters of order in France were called La Grande Chartreuse, the Priory became known as the Charterhouse. Old illustrations show a few small buildings around the Priory Church, surrounded by a wall and moat.  Roads led southwards towards the town walls and eastwards (now Charterhouse Lane) to join the road linking High Street near North Bridge with the village of Sculcoates (now Wincolmlee). This Carthusian Priory was one of only seven built in England, as the order was not particularly attractive. The monks shut themselves away from the world and also each other, spending most of their time in their own cell, only meeting once a week for a communal service and meal.

In 1377, Michael De La Pole became the Lord of the Manor of Sculcoates and, two years later, he gave it to the Charterhouse. He also made several other grants of land to the Priory over next few years so that the Charterhouse held an important and influential position in Sculcoates. The De La Poles retained links with the Charterhouse for some time after this and several members of the family instructed that their bodies were to be buried in the Priory church. In the 18th century, workmen who were building houses in Sykes Street (which was on the site of the Priory) came across the foundations of thick walls and a quantity of human bones which were thought to belong to members of the De La Pole family.

Initially the Priory also housed a few poor men and women but in 1383, a separate almshouse was provided for 13 poor men, 13 poor women and one priest (the Master) who was in charge of it. It was also known as the Charterhouse Hospital, Maison Dieu or God's House Hospital. In 1536, the Priory was dissolved by Henry VIII, re-established following year and finally closed in 1539. The Almshouse escaped as it had a separate charter. At the Dissolution, the Corporation of Hull acquired land in Sculcoates and also became responsible for appointing the Master.of the Charterhouse Hospital. The Charterhouse buildings were not totally demolished at the Dissolution. Some were inhabited by various people including the Aldred family who held part of the Manor of Sculcoates.