Son of a valet, he was educated at the College des Quatre Nations in Paris. After completing his studies, he went to Spain at the court of Charles III. After the king left for Italy, he was commissioned to take care of the affairs of Philip of Bourbon, becoming a private secretary, custodian of his private fund and organizer of parties and shows in Chambéry and elsewhere. In June 1749 he was transferred from Paris to Parma as an observer and adviser to Philip, recommended by the same Louis XV of which Philip was son-in-law. In order to show him his utmost trust, the duke appointed him, on 26 June 1749, General Intendant of the House, entrusting him with the services of the Royal House, payments of expenses and salaries, the intention of the palaces, villas, gardens and theaters, the direction of shows and festivals, accommodation organization.
Philip, always grateful for the service offered to him by Guillaume, made him Minister for Foreign Affairs and Foreign Affairs, giving him the post of Prime Minister in 1759. With his activities he made the duchy more flourishing under the guidance of a good administration. On 20 June 1764, being named Marquis of Felino, he was entrusted with the lands of Felino and San Michele Tiorre.
While reorganizing the Public Library of Parma, he established a private one for himself, including among the many volumes of the Encyclopédie. Thanks to his commitment, the Academy of Fine Arts of Parma, the Museum of Antiquities and the Royal Printing House were born and the University of Parma was strengthened. In order to implement his ambitious cultural and propaganda plan he tried to attract to Parma intellectuals and artists, among whom Condillac, who was entrusted with the education of the prince Ferdinando, Paolo Maria Paciaudi, who would become curator of the Palatina Library, the Saluzzo Giovanni Battista Bodoni, a typographer destined to become a point of reference for the worldwide printing art, Jean-Baptiste Boudard, a sculptor who made many of the plastic works still scattered in the Ducal Garden, and Ennemond Petitot, the Lyon architect who was entrusted the urban restructuring of many points of the city: the Church of San Pietro (with the reconstruction of the facade), the Governor's Palace in the central Piazza Grande (today Piazza Garibaldi), the Palazzo di Riserva where the Ducal Theater, the Casino of the Stradone (which later took its name), and the Ducal Palace of the Garden, rearranged with Boudard. In 1756 Du Tillot called to court the French gentleman Guillaume Rouby de Cals: initially employed by the finance administration, he then became his private secretary and director of the first military fabric factory and for the royal house founded in Borgo San Donnino (today Fidenza ). All these efforts were valid for the city of Parma, at that time, the definition of Athens of Italy , also in virtue of the great expansion that Arcadia found there (the so-called "third Arcadia") in which it first operated place Carlo Innocenzo Frugoni. He had the city's cadastre compiled and renovated the Ducal Garden according to the Versailles model.
His secular and purposely pro-Italian management of the Duchy of Parma gave him severe conflicts with the Pontifical State, both for appointments made and for the conferral of mandates, but above all because of the suppression of the Inquisition and the expulsion of the Jesuits from the Duchy. With the new regency of Ferdinand of Bourbon and the arrival of Maria Amalia of Hapsburg-Lorraine, his work began to undergo a severe re-examination, which forced him first under house arrest in Colorno (where he resided) and then fleeing in 19 November 1771 to Spain, then return to France where he died in 1774. He was replaced by the Spaniard Jose de Liano in the role of Prime Minister of the Duchy.