Natoire's artistic activity is documented equally in Paris and in Rome. Having spent six years in Italy (1723 to 1729) as a 'pensionnaire' at the French Academy in Rome, he returned in 1751 as a follower of F. de Troys to the Académie de France and served as its director until 1774. During his Roman years, he produced one of his major works, the ceiling painting 'The Apotheosis of St Louis' in the church of San Luigi dei Francesi.
His previous activity in Paris during the more than twenty years between 1729 and 1751 is documented in numerous decorations of private and public buildings. Despite all his recognition and popularity, Natoire stood in the shadow of his contemporary F. Boucher, with whom he had shared an apprenticeship under F. Le Moyne before both were inducted into the academy in 1734 and named professors in 1737.
In his series of paintings (the best known being the 'Story of Amor and Psyche' in the Hôtel Soubise, 1739-1742) and in his designs for the Gobelins, he managed to incorporate the most important genres - history, religion, and mythology - into his decorative programs in equal measure.
Despite his adaptation to the preferences and taste of the public, Natoire's painting even in his Paris years was primarily defined by a seemingly classical compositional style, and was therefore more reserved and less successful than the works of Boucher, which wholly emphasised sensuality.
For his drawings, Natoire favoured blue-toned paper and crayon and brush, with which he lent his sheets a distinctly painterly quality.