Toll-like receptors (TLRs) are transmembrane receptors composed of extra cellular leucine rich repeats (LRRs) that identify specific pathogen associated molecular patterns triggering a innate immune cascade. The LRR regions of TLR 1–10 proteins of goat (Capra hircus), sheep (Ovis aries), buffalo (Bubalus bubalis) and bovine (Bos taurus) were modeled using MODELLER 9v7 tool and validated. The similarities and variations of these 10 TLRs extracellular regions of each species were compared using online servers like FATCAT, SSM and SSAP. It was evident that the LRRs of TLRs like 1, 2, 3 and 6 showed structural convergence with <1 % RMSD deviation while TLRs like 5, 7, 8 and 9 had high divergence. Docking analysis showed that TLR 2, 3 and 7 of all the selected four ruminant species were able to bind with their corresponding ligands like Peptidoglycan (PGN), Poly I:C, Resiquimod (R-848) and Imiquimod. However, there were variations in the active site regions, interacting residues and the number of bonded interactions. Variations seen among TLR structures and their ligand binding characteristics is likely to be responsible for species and breed specific genetic resistance observed among species or breeds.