Desmarest was the son of a school teacher from Soulaines-Dhuys in France. He first came to notice when he won a prize essay set by the Amiens Academy in 1751 on whether England and France had ever been joined together. Working for a while in Paris as an editor of scholarly works, he eventually started work for the department of commerce in 1757 investigating and reporting on various trades and industries. He served as inspector-general of manufactures (1788–91).

In 1763, following the work of Jean Guettard, he noticed large basalt deposits and traced these back to ancient volcanic activity in the Auvergne region. He mapped the area and worked out the geology of the volcanoes and their eruptions in great detail, publishing his work in the Encyclopédie of 1768. This work disproved the theory that all rocks were sedimentary by revealing basalt's igneous origins. He later produced an influential work, Géographie physique (1794; Physical Geography).