Grignard was the son of a sailmaker. He was described as having a humble and friendly attitude. After attempting to major in mathematics, Grignard failed his entrance exams before being drafted into the army in 1892. After one year of service, he went back to pursue mathematics at the University of Lyon and finally obtained his degree Licencié ès Sciences Mathématiques in 1894. In December of the same year, he transferred to chemistry and began working with Professors Philippe Barbier (1848–1922) and Louis Bouveault (1864–1909). After working with stereochemistry and enines, Grignard was not impressed with the subject matter and asked Barbier about a new direction for his doctoral research. Barbier advised that Grignard study how a failed Saytzeff reaction using zinc, was successful, in low yields, after substitution of magnesium. They sought to synthesize alcohols from alkyl halides, aldehydes, ketones, and alkenes. Grignard hypothesized that the aldehyde or ketone prevented the magnesium from reacting with the alkyl halide, accounting for the low yields. He tested his hypothesis by first adding an alkyl halide and magnesium filings to a solution of anhydrous ether and then adding the aldehyde or ketone. This resulted in a drastic increase in the yield of the reaction.
A couple of years later, Grignard was able to isolate the intermediate. He had heated a mixture of magnesium turnings and isobutyl iodide and added dry ethyl ether to the mixture, observing the reaction. The product is known as a Grignard reagent. Named after him, this organo-magnesium compound (R-MgX) (R = alkyl ; X = Halogen) readily reacts with ketones, aldehydes, and alkenes to produce their respective alcohols in impressive yields. Grignard had discovered the synthetic reaction that now bears his name (the Grignard reaction) in 1900. In 1901, he published his doctoral thesis titled "Thèses sur les combinaisons organomagnesiennes mixtes et leur application à des synthèses d‘acides, d‘alcools et d‘hydrocarbures". He became a lecturer in organic chemistry at the University of Nancy in 1909, and was promoted to full professor in 1910. In 1912 he and Paul Sabatier (1854–1941) were awarded the Nobel Prize in Chemistry. During World War I he studied chemical warfare agents with Georges Urbain at Sorbonne University, particularly the manufacture of phosgene and the detection of mustard gas. In 1918, Grignard discovered that sodium iodide could be used as a battlefield test for mustard gas. Sodium iodide converts mustard gas to diiododiethyl sulfide, which crystallizes more easily than mustard gas. This test could detect as little as 0.01 gram of mustard gas in one cubic meter of air and was successfully used on the battlefield. His counterpart on the German side was another Nobel Prize–winning chemist, Fritz Haber.
Grignard died on 13 December 1935, in Lyon at the age of 64.