The oldest of ten children, he refused to exercise the right of the first-born son to the majority of his parents' wealth.

He served under Jean Baptiste Kléber in the army of Sambre-et-Meuse, losing his left leg to a cannonball on December 17, 1795, but continuing in the army with a wooden leg, and joined Kléber on the Egyptian campaign.

He was elected a member of the Institut d'Égypte's political economy section on February 13, 1796[citation needed], in the class of moral and political science, and formed part of the commission for drafting the institute's regulations.

He was just starting to learn to write with his left hand when gangrene struck, causing a fever that killed him.

Napoleon wrote of him in the order of the day: "Our universal regrets accompany General Caffarelli to the grave; the army is losing one of its bravest leaders, Egypt one of its legislators, France one of its best citizens, and science, an illustrious scholar."