As a disease of domestic ruminants, fascioliasis is of considerable economic importance. The current research adopted two main methods for diagnosis of fascioliasis in naturally infected cattle and buffaloes. Antibody and antigen detection were compared with the conventional parasitological examination. A total of 139 Egyptian buffaloes and 80 native breed cattle were examined parasitologically for Fasciola eggs detection in faeces. The serum samples of animals were examined for antibodies detection to excretory/secretory products, adult worm extract and egg antigen by indirect ELISA. These samples together with faeces of the same animals were investigated by sandwich ELISA for circulating and coproantigen detection respectively. The results proved that antibody and antigen detection by far better than parasitological examination. Moreover, antibody detection to excretory/secretory (ES) products is more sensitive (68.9%) in the diagnosis of fascioliasis than to adult worm extract (64.8%) and to egg antigen (57.9%) in the examined animals. Furthermore, circulating antigen detection assay is preferable (66.7%) than antibody detection assays to both adult worm and egg antigen in the total examined bovines. While antibody detection assay to ES products recorded higher infection rate (68.9%) than circulating antigen detection one. These comparative diagnostic potentials are also observed in buffaloes but with different infection percentages. It is worthy to note that in cattle, detection of circulating antigen recorded infection percentage higher than that recorded using antibody detection assays to ES products, adult worm and egg antigens. Coproantigen detection assay possesses the highest immunodiagnostic potential for fascioliasis either in cattle or in buffaloes than any other assays introduced in the present study and recorded infection percentage reached to 81% in the total bovines. In conclusion, the current research recommended a combination of both coproantigen detection assay and antibody detection test to ES products for fascioliasis diagnosis in buffaloes, while in cattle, circulating and coproantigen detection assays are recommended.