It was founded in 1319 or 1320 as Monte Oliveto with reference to the Mount of Olives and in honour of Christ’s Passion. This is the mother-house of the Olivetans and the monastery later took the name of Monte Oliveto Maggior (‘the greater’) to distinguish it from successive foundations at Florence, San Gimignano, Naples and elsewhere.
The cloister is famous for the series of frescoes illustrating scenes from the legend of St. Benedict begun by Luca Signorelli (1497–1498) and completed by il Sodoma (1502 or 1505). The church and library contain fine inlaid woodwork by Fra Giovanni da Verona.
The monastery is described by Pope Pius II in his Commentaria. Nicholas of Cusa visited the monastery in the same period and preached his last extant sermon at the clothing of a novice with the order's habit.