A comparative study of the leaflets of two domestic species of Prosopis is reported. Both the species, Prosopis cineraria and Prosopis juliflora, have been reported to possess antibacterial, antifungal, anti-inflammatory and the most concerning anticancer properties. In view of its medicinal importance and taxonomic confusion, the individual morphological and histological characteristics of these two species have been described through certain parameters such as structural profile of the leaflets, stomatal morphology, venation pattern, petiolule and vascular system of the rachis. Evaluation of the fresh and anatomical sections of the leaves of both species was carried out to determine its macro- and microscopical (histological) characters. The studies indicated the presence of bipinnately compound leaf, an entire margin, apiculate apex, obtuse base, reticulate venation, thick and straight anticlinal walled epidermal cells, prismatic type of calcium oxalate crystals in the mesophyll tissue, dense deposition of tannin content and paracytic type stomata in the P. cineraria, whereas P. juliflora has a bipinnately compound leaf with an entire margin, blunt apex, round base, reticulate venation, thick and straight walled epidermal cells, large mucilage cavities in the mesophyll tissue and paracytic type stomata. The above findings provided referential information for identification of the species P. cineraria and P. juliflora.