AbstractA 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.