Commerçon was born at Châtillon les Dombes in France. He studied medicine and botany at Montpellier, and for a time was a practicing physician. At the request of Carolus Linnaeus, Commerçon collected and categorized fish of the Mediterranean on behalf of the museum in Stockholm. Commerçon returned to live at Châtillon les Dombes in 1756 and there occupied himself in creating botanical gardens.

In 1766, Commerçon joined Bougainville on his voyage of circumnavigation. Among the wildlife that Commerçon observed was a particular kind of dolphin in the Strait of Magellan. The animal is now known as Commerson's Dolphin.

It was not until the expedition reached Tahiti that Commerçon's servant on the voyage, Jeanne Baré, was discovered to be a woman. In spite of Commerçon's apparent lack of perceptiveness concerning Baré, he was an astute observer of the Tahitian people and culture, thanks in part to a remarkable lack of European prejudice compared to other early visitors to the island. Commerçon and Bougainville together were responsible for spreading the myth of Tahitians as the embodiment of the concept of the noble savage. Commerçon also studied and collected plants wherever the expedition stopped. On the return voyage to France, he remained behind at the island of Mauritius, in order to botanize there and on Madagascar.

Commerçon died at Mauritius at the age of 45.