Due to his intelligence and loyalty, Harrison became a trusted agent of the Grand Master Reginald Birch. He was tasked with meeting Templar allies across the world, such as Duarte Jorge Correia Pinto, Alonso Fernández de Heredia and Magdelaine Lévesque. Harrison was also involved in coordinating the Order's major operations, including the search for the Grand Temple in the American colonies, and the Prophecy Disk in Chichen Itza.
In 1742, Harrison was stationed in Manila to look for Precursor sites in China. While he had no luck finding any sites, he did find a lead on the Precursor box. In a letter he sent to Reginald Birch, he suggested starting a war in Europe to find the box. The following year, Lourenço de Noronha contacted Harrison stating that searching for Precursor sites and artifacts in central Africa would be a good idea. However, de Noronha needed to settle the unrest within the region before anything could be done.
Around 1746, Harrison contacted Duarte Jorge Correia Pinto in Portugal. Harrison instructed Pinto to conduct a search for a Precursor site around Lisbon. However, Pinto had no luck finding a site. Two years later, Harrison, now stationed in Calcutta, sent a letter to William Johnson asking for aid in hunting down the Assassins in the area and weakening the Kingdom of Mysore so that the East India Company could prosper.
In 1751, Harrison moved to Goree Island. There, he wrote a letter to Reginald Birch insisting that slavery operations should cease, as people found out about their operations. Harrison went on to suggest using slaves from the French or Spanish colonies nearer to Chichen Itza. Harrison also suggested moving command of the Chichen Itza excavation from Florida to Louisiana under Madeleine de L'Isle's supervision, and to promote her to the rank of Master Templar as a reward for her services.
On 18 April 1754, Haytham Kenway murdered the Assassin Miko at the Theatre Royal in London, and acquired the amulet in his possession. Birch explained that the amulet served as the key to the Grand Temple, that he had spent decades searching for. Harrison used his skills to narrow down the location of the temple, and told Haytham that it was located somewhere in the northern part of the colonies, most likely New York or Massachusetts area. Subsequently, Haytham set off to locate the Grand Temple and acquire its contents for the Templars.
In 1757, Haytham learned that Birch was the man responsible for the murder of his father, Edward, in Haytham's youth. On 9 October, Haytham and his half-sister Jenny arrived at Birch's home in Troyes, France, to confront the Grand Master, but Harrison stood in their path. He attacked Haytham with a pistol at the house's stairwell, but Haytham dodged the shot and proceeded to grapple Harrison to the floor to demanded answers from him. As Harrison remained silent, Haytham responded by killing him with his Hidden Blade.
- In 2015, Harrison's name was on a list of known British Templars used by the Templar Isabelle Ardant.
- Assassin's Creed III (first appearance)
- Assassin's Creed: Forsaken
- Assassin's Creed: Rogue (mentioned only)