Knowsley was held by the Lathom family since the twelfth century. In 1385, with the marriage of Isabel de Lathom to Sir John de Stanley the lands passed to the Stanley family who still hold it today.
Sir John Stanley was made Lord Deputy of Ireland by Richard II and went on to hold a number of distinguished positions including Lord Lieutenant of Ireland, Treasurer of the Royal Household and Lord of the Isle of Man. His grandson Thomas also became Lord Lieutenant of Ireland, and in 1456 was summoned to Parliament as Lord Stanley. The second Lord Stanley (another Thomas) was knighted in 1460 and was created the First Earl of Derby by a grateful King Henry VII after his intervention proved decisive in the Battle of Bosworth in 1485.