Andrea Appiani was born in Milan in 1754, the son of physician Antonio and Marta Liverta. In 1768, his father enrolled him in the drawing school of the Accademia Ambrosiana. There, Appiani met Gaetano Monti, a future sculptor and close friend, and developed an interest in the art of the sixteenth century. At the academy, he learned the proportions of the human body, figure composition, and practiced drawing using three-color pencils and blending tools.

From 1769 to 1775, Appiani underwent years of intense training. After studying at Giudici's school, he attended the Life Drawing School at the Accademia Ambrosiana, copying works of great masters and comparing them with nature to redraw subjects from life. Through this process, he refined his style and began to move away from the Baroque tradition. He later studied anatomy for nine years at Milan’s Ospedale Maggiore, deepening his understanding of the human body.

Appiani's early years, from 1772 to 1775, were marked by financial difficulties, leading him to paint flowers on paper and silk. During this period, he produced a series of works that have since been lost.

Between 1780 and 1782, Appiani participated in the decoration of the Archducal Palace of Milan. In addition to his frescoes for aristocratic residences, he gained recognition as a skilled portraitist of important figures, including Napoleon, Vincenzo Monti, and Antonio Canova. Under Napoleon, he would earn the title of "first fresco painter of Europe."

In 1800, Appiani was appointed Commissioner for Fine Arts, but his career truly flourished during the Napoleonic occupation, which granted him prestigious commissions and official roles. One of his most significant achievements was his appointment as "Premier Peintre" of Napoleon in 1805, a position that made him the leading figure in the French government's celebratory artistic policies.

After being named Curator of the Royal Gallery of Brera, Appiani passed away in Milan on November 8, 1817, due to a cerebral hemorrhage.