We report Pd-catalyzed direct C-H arylation of thiazole, where the regioselective outcome is controlled by the appropriate selection of a base and a ligand. Employing Pd/PPh3/NaOtBu in the reaction with a broad range of aryl halides affords access to C2-arylated thiazoles with high yields. Conversely, a catalytic system comprising a Pd catalyst, Bphen (bathophenanthroline), and K3PO4 provides various C5-arylated thiazoles. These catalytic conditions enable sequential arylation at positions C5, C2, and C4 of thiazole, providing a streamlined approach to the synthesis of 2,4,5-triarylated thiazole scaffolds. Our computational models for C-H bond cleavage exhibit subtle differences from the well-established carbonate-assisted nCMD mechanism. We found that the interplay of stabilizing and destabilizing interactions between the Pd catalyst and the reacting partners, namely, thiazole and the aryl group, in the critical transition states directs the reaction toward C2 arylation. Furthermore, our study reveals that the C2 and C5 arylation of thiazole may proceed through different pathways involving either monometallic or bimetallic complexes. The pathway involving the bimetallic complex, which is inaccessible for C2 arylation, represents the lowest-energy route for the C5 arylation of thiazole.