Born at Cherbourg in northern France, Grignard first studied mathematics at the University of Lyons before he switched to chemistry. He was a lecturer at the universities of Besançon, Nancy, and Lyons before he was appointed professor of chemistry at Nancy in 1910. In 1919 he moved to the chair of chemistry at Lyons.

In 1901 he discovered an important class of organic reagents now known as Grignard reagents. For this work he shared the Nobel Prize for chemistry with Paul Sabatier in 1912. He was searching for a catalyst for a methylation reaction he was trying to induce; chemists had earlier tried to use zinc in combination with various organic compounds and found it moderately successful. Grignard used magnesium mixed with organic halides in ether solution and obtained compounds of the type RMgX, where X is a halogen (Cl, Br, I) and R an organic group. These Grignard reagents are very versatile and permit the synthesis of a large number of different classes of compounds, particularly secondary and tertiary alcohols, hydrocarbons, and carboxylic acids.

In 1935 he began the publication of his Traité de chimie organique (Treatise on Organic Chemistry), which was continued after his death and is now a massive multivolume work.