Messier specialized on comet hunting, and observed 44 of them during his professional life (plus at least one - the great comet of 1744, described by De Cheseaux - which he had observed from Lorraine in young years). Of these he had originally discovered 13 or 14, and independently co-discovered another about 6.

His most important work, however, was the compilation of his Catalogue of Nebulae and Clusters of Stars, which he created in order to list those nebulous objects which might be easily confused with comets, in the telescopes of his days. The final published version of the catalog contained 103 entries, but the modern version of this list has been extended to 110 objects, the seven additional objects added from notes of Charles Messier and Pierre Mechain, who at that time collaborated with him. Of these deepsky objects, Messier originally discovered 39 or 40, and independently re- (or co-) discovered at least 10; Pierre Mechain originally discovered 29 and co-discovered 1 of the objects in Messier's catalog.