Little information survives about the early grammar school: it would have taught a Latin curriculum to boys from Dundee and the surrounding area.

Early scholars included Hector Boece, historian and first principal of the University of Aberdeen; William Wallace; and James, John and Robert Wedderburn, authors of The Gude and Godlie Ballatis, one of the most important literary works of the Scottish Reformation.

Greek was added to the curriculum shortly after 1562, under the Master Alexander Hepburn, who would author Grammaticae Artis Rudimenta Breviter et Dilucide Explicata, a Latin primer, in Dundee, and become bishop of Ross in 1574.

[3] The school moved into its first permanent home in 1589, a building in St Clement's Lane demolished to make way for the City Square in the 1930s.

Among the masters here were Andrew Duncan, an academic and Presbyterian minister, and David Lindsay, later Bishop of Edinburgh, who crowned Charles I at Holyrood.

[3] In 1785, Dundee Academy was opened in the Nethergate, in a hospital building built by the Trinitarian Friars before the Reformation; today it is the site of St Andrews Roman Catholic Cathedral.

Its first rector, James Weir, described as "a gentleman of considerable abilities, but rather a projector", took great interest in the problem of perpetual motion.

The academy re-opened in 1801, under Thomas Duncan, a brilliant mathematician: but after his appointment to the Regius Chair of Mathematics at the University of St Andrews in 1820 the school suffered.

The situation was worsened by a similar Act in 1878, and legal action looked inevitable, until an alumnus, William Harris, offered, in February 1881, to donate £30,000 for the purposes of higher education in Dundee on condition that the board give up all claim to the school.

Thanks to Margaret Harris, who waived her right to a life-rent of her brother's estate, a girls' school was built across Euclid Crescent in two stages between 1886 and 1890.

Mayfield has undergone massive investment in recent years with new sports facilities, and is the home of Dundee High School Former Pupils' RFC; it is also let out to other groups.

In 2019, the school was required to pay £60,000 as a result of unfairly dismissing the principal teacher of religious, moral and philosophical studies.

[6][7] Judge Ian McFatridge said that evidence from Dr Halliday and Lise Hudson, his deputy and named successor, was not credible or reliable: the school did not contest the ruling.