An ancient foundation, the school existed before the Reformation as the chantry school of St Mary's Church, Truro. In 1549, following Edward VI's Dissolution of Colleges Act 1547 which suppressed all chantries, the school was refounded and took on a new identity as Truro Grammar School. However, as reported by Nicholas Carlisle in his survey of 1818, "The Grammar School at Truro owes its origin and endowment to some benevolent person, whose name is now not known." The best evidence of the refounding of the school is an entry in the Journal of the House of Commons dated 21 May 1689, which refers to the grammar school being founded by a deed, since lost, of the third year of King Edward VI.
In 1767, the Rev. St John Eliot, a former Rector of Truro, founded two Exhibitions tenable only at Exeter College, Oxford, worth £30 a year each, with preference to be given to boys from the school. In 1818 Carlisle reported that over the previous ten years the number of scholars had been about fifty and that The School is a venerable Structure, 42 feet in length by 28 feet in breadth, and 18 1/2 feet in height to the ceiling, with pillars and pilasters of the Corinthian order. Adjoining, is a Library, filled with excellent editions of the Classics and other valuable Works, which are under the sole control of the Master... The Eton Latin and Greek Grammars are at present in use; and the system of Education is similar to that of ETON COLLEGE.
In the early 19th century an "anniversary school meeting" took place on every second Thursday in September, being a gathering of the school's former pupils. Cyrus Redding, in his An Illustrated Itinerary of the County of Cornwall (1842) called Truro Grammar School "the most celebrated school in the county".
With the creation of the Diocese of Truro in 1876 from the Cornish part of the old Diocese of Exeter, the 16th-century parish church of St Mary's was designated as a cathedral. The church was then partly demolished and partly incorporated into the new neo-Gothic Truro Cathedral, built on the same site. The pupils of the old grammar school had worshipped at St Mary's and became responsible for providing the new cathedral's choristers. It thus began to be known as the "Cathedral School".
In 1906 the school was established as Truro Cathedral School by the Dean and Chapter as a Church of England public school. By the early 20th century the school was a private school and had a boarding house called Trewinnard Court. The buildings were designed by the cathedral architect F. L. Pearson and built in the precincts of the cathedral. In 1925 the headmaster resided at Trewinnard Court. At that time choristers paid no tuition fees and there were two Bray scholarships open to choristers worth £30 p.a. The Hawkins scholarship worth £80 p.a. was open to former pupils studying at a university and tenable for three years. By the 1920s the cathedral school's reputation had significantly increased.