In early times one group of islands was in the possession of a confederacy of hermits. King Henry I gave it to Tavistock Abbey which established a priory on Tresco; it was abolished at the Reformation. The priory was given the care of souls in the secular islands by the lord of the fief. In 1233, a prior here, known as Alan of Cornwall, was made abbot of Tavistock.
The island is named as Trescaw in an 1814 publication, and was described as 'St. Nicholas' when confirmed as a grant to the abbot of Tavistock by pope Celestin in 1193.
The island is administered for the crown by the Duchy of Cornwall and is leased to the Dorrien-Smith estate, which runs it as a timeshare business. The Dorrien-Smith family (descended from Augustus Smith) held the position of Lord Proprietors of the Scilly Islands between 1834 and 1920.
From 2001 until 2009, the island hosted a marathon run organised in aid of Cystic Fibrosis. The course consists of 7½ laps around the island. The event is always held on the same day as the London Marathon. Past winners include Dara O'Kearney and Bob Brown
In 2007 a rebuild of the Abbey Farm/Shed area was completed; this area served as RNAS Tresco, a seaplane base during the First World War. The development included rental cottages, a swimming pool, a health centre and the "Flying Boat Club" restaurant.