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Palladium catalysts have recently been discovered that enable the directing group-free C–H activation and functionalization of arenes without requiring an excess of the arene substrate. By overcoming this long standing challenge, the resulting synthetic methods have now become suitable for the functionalization of complex organic molecules. The key to success in several of these transformations has been the use of two complementary ligands, an N-acyl amino acid and an N-heterocycle. Further applications of this design principle will likely require the guidance by a profound mechanistic understanding. This prompted us to engage in a detailed experimental and computational mechanistic study of the dual ligandenabled C–H activation of arenes. Based on comprehensive kinetic experiments, (CID-)MS and DOSY-NMR measurements, and DFT calculations we find that a 1:1:1 complex of palladium and the two ligands is the active species that enables a partially rate-limiting concerted C–H activation as part of a PdII/Pd0-cycle. Our study highlights the importance of catalyst speciation and allows us to rationalize the role of each ligand as well as the observed regioselectivities. These findings are expected to be highly useful for further method development using this powerful class of catalysts.