Having risen to the position of Prior of the Langue of Auvergne, he was elected 44th Grand Master of the Order in 1521.

He commanded the Order during Sultan Suleiman's long and bloody Siege of Rhodes in 1522, when 600 knights and 4500 soldiers resisted an invading force of about 100,000 men for six months,[1] but eventually negotiated the capitulation and the departure of the knights on New Year's Day 1523 to Crete.

He then led the Order during several years without a permanent domicile—first Kandi on Crete, then successively Messina, Viterbo and finally Nice (1527–1529).

L'Isle-Adam took formal possession of the islands on 13 November, when the silver key of the capital Mdina was given to the Grand Master.

[2] L'Isle-Adam died at the Our Lady of Jesus convent (ta' Ġieżu) in Rabat, Malta on 21 August 1534.