He was born in Dundee where he attended school. Later he left to study at the University of Paris where he met Erasmus, with whom he became close friends while they were both students. By 1497 he had become a professor of philosophy at the university.
In 1500, he was induced to leave Paris for Aberdeen by a generously financed offer to become the first principal of the newly established University of Aberdeen, created at the behest of James IV by William Elphinstone, Bishop of Aberdeen under the authority of a Papal bull issued by Pope Alexander IV.
From then onwards, he worked closely with Elphinstone, to set up the new university and by 1505, regular lectures were taking place at King's College. The university structure was modelled on those of Paris and of Orlèans. As intended, Boece was installed as the first principal of the university and gave lectures on medicine and on divinity.
Apart from his work on creating the university, Boece also wrote and published two books, one of biography and one of history. In 1522 he published the Vitae Episcoporum Murthlacensium et Aberdonensium (Lives of the Bishops of Murthlack and Aberdeen) and in 1527 the Historia Gentis Scotorum (History of the Scottish People). The latter is his most famous publication. It was only the second scholarly history of the Scots to be written. By modern standards it is overly patriotic and has many inaccuracies. However it was very well received at the time, both in Europe and in Scotland after its translation from Latin into French and then in 1536 from Latin into Scots. This is the oldest book of prose written in Scots to survive into modern times and was the source of the story of Macbeth used by Raphael Holinshed and later by William Shakespeare.
At the end of 1534, Boece became Rector of Fyvie. He died in Aberdeen two years later at the age of 71.