Donald MacKinnon was educated at Cargilfield School, Edinburgh (1921–26), Winchester College (1926–31) and New College, Oxford (1931–35), where he also held a scholarship and graduated in both Greats and Theology. After Edinburgh, MacKinnon became a fellow and tutor at Keble College, Oxford (1937–47), and held the Wilde lectureship in Natural and Comparative Religion (1945–47). At the age of thirty-four MacKinnon was appointed to the Regis chair of Moral Philosophy in Aberdeen University (1947–60). As a teacher of large ordinary classes in his subject, he influenced generations of undergraduates. He completed an important monograph, A Study in Ethical Theory (1957), before taking up the Norris-Hulse chair of Divinity in Cambridge (1960–76). For fifteen years MacKinnon dominated Cambridge theology.

MacKinnon's renown as a speaker was demonstrated by invitations he accepted to deliver named lecture series in Cambridge, Exeter, Aberystwyth, the London School of Economics, Newcastle and Stirling. He served as president of the Aristotelian Society and president of the Society for the Study of Theology. After retiring from Cambridge in 1976 he taught in St Andrews for one session during the interregnum in the chair of divinity, before returning to Aberdeen. Collections of essays appeared as Borderlands of Theology (1968), Explorations in Theology (1979), and Themes in Theology, the Three-Fold Cord (1987). Much in demand as a conference speaker, MacKinnon travelled extensively and served inter alia on the theological commission charged with drafting papers for the General Assembly of the World Council of Churches in 1954.

MacKinnon was elected a fellow of the British Academy in 1978 and a fellow of the Royal Society of Edinburgh in 1984. He was awarded honorary degrees by the universities of Aberdeen, Edinburgh and Stirling. Following a sudden heart attack, he died in Aberdeen Royal Infirmary on 2 March 1994.