In this study the morphological and anatomical variation in stem and leaf tissues of three genera of Zygophyllaceae: Fagonia (4 taxa), Tetraena (4 taxa), and Tribulus (4 taxa) were investigated. The twelve examined taxa included nine species that grow in the eastern region of Saudi Arabia. Additional features for taxon identification and characterization can be developed because of our findings. The anatomical features investigated included, stem diagram, epidermal cell shape, structure of cortex and pith, the number of vascular bundles, petiole and blade outline in cross section, mesophyll type, and distribution of secretory tissues and crystals. The conclusions of this study show that anatomical features, particularly the petiole and blade outlines and the type of vasculature of the stem and petiole, are significant tools in identifying and distinguishing between the species examined and can provide a key for identification of the investigated taxa. Distinction of the investigated Zygophyllaceae species, based on the characters assessed in this study, agreed with previous classifications of these species.