A class of 2-hydroxypyridine based ligands are explored to achieve enhanced catalytic activity for ortho-C-H bond activation/arylation reaction over [(η6-p-cymene)RuCl2]2 catalyst in water. Extensive studies using a series of substituted 2-hydroxypyridine based ligands (L1 – L6) inferred that 5-trifluoromethyl-2-hydroxypyridine (L6) exhibited favorable effects to enhance the catalytic activity of Ru(II) catalyst for ortho C-H bond arylation of 2-phenylpyridine by 8 folds compared to those performed without ligands. The (η6-p-cymene)Ru – L6 system also exhibited enhanced catalytic activity for ortho C-H bond arylation of 2-phenylpyridine using a variety of aryl halides. NMR and mass investigations inferred the presence of several ligand coordinated Ru(II) species, suggesting the involvement of these species in C-H bond activation reaction. Further in concurrence with the experimental findings, the density functional theory (DFT) calculations also evidenced the prominent role of 2-hydroxypyridine based ligands in Ru(II) catalyzed C-H bond arylation of 2-phenylpyridine with lower energy barrier for the C-H activation step.