He was taken on as a young man by the antiquarian and historian of architecture, Charles-Alexis-Adrien Duhérissier de Gerville, who engaged him to copy manuscripts in his collection, and taught him enough of the basics of paleography that he was able to gain entrance to the École des Chartes in 1846.
Delisle proved that the bulk of the manuscripts of French origin which the Earl of Ashburnham had bought in France, particularly those bought from the book-seller Jean-Baptiste Barrois, had been purloined by Count Libri, inspector-general of libraries under King Louis-Philippe, and he procured the repurchase of the manuscripts for the library, afterwards preparing a catalogue of them entitled Catalogue des manuscrits des fonds Libri et Barrois (1888), the preface of which gives the history of the whole transaction.
After his retirement (21 February 1905) he brought out in two volumes a catalogue and description of the printed books and manuscripts in the Musée Condé at Chantilly, left by the duc d'Aumale to the French Institute.
The thirty-second volume of the Histoire littéraire de la France, which was partly his work, is of great importance for the study of 13th and 14th century Latin chronicles.
Delisle was undoubtedly the most learned man in Europe with regard to the Middle Ages; and his knowledge of diplomatics, palaeography and printing was profound.
He was motivated to a great extent by the destruction the French Revolution had brought upon medieval manuscripts and buildings; for Delisle, the publication of texts was necessary not only for the preservation of the past but also of civilisation.