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Boissonade entered pubic service under General Charles François Dumouriez (1739-1823), the Minister of Foreign Affairs, but was driven out in 1795. When Lucien Bonaparte, as president of the Council of Five Hundred, restored Boissonade, who served as secretary to the prefecture of the Upper Marne. He then left public life and on the basis of his edition of the Heroicus of Philostratus, gained a position in Greek at the University of Paris beginning in 1809. In this period he published the first edition of Maximus Planudes' translation of Ovid's Metamorphoses then compiled a series of annotated editions of the Greek poets in 24 volumes in only nine years. In 1813 he succeeded Pierre Henri Larcher (1726-1812) as professor of Greek and in 1828 Jean-Baptiste Gail (1755-1829) at the Collège de France.  Called by Wilamowitz a "useful all-rounder," Boissonade did not confine himself to Greek prose of the later Roman Empire, but edited Aristophanes and devoted a large part of his later career to the Greek Anthology. Nevertheless, he is chiefly remembered for his editio princeps of Babrius of the Anecdota Graeca, which is of great value for Byzantine studies and as an editor of late Greek prose.  Sandys reports that his first lecture at the Collège de France was devoted to the first three words of Plato's Ion. "He seldom lectured on any author so late as Plutarch, while he seldom edited any author so early. It is to be remembered to his honour that, but for his editorial aid, many of the minor Greek authors might still have been buried in oblivion."

Following his death a collection of his papers was prepared after his death by Ferdinand Collincamp.