Amides are important functional synthons that have been widely used in the construction of peptides, natural products, and drugs. The C-N bond cleavage provides the direct method for amide conversion. However, amides, especially secondary amides, tend to be chemically inert due to the resonance of the amide bond. Here, we describe an efficient Pd-catalyzed transamidation and decarbonylation of multiamide structure molecules through C-N bond cleavage with excellent chemoselectivity. The transamidation of secondary amides and the decarbonylation of phthalimide provide meaningful tools for the modification of amino acid derivatives. Moreover, further transformations of azidation and C(sp3)-H monoarylation emphasized the potential utility of this selective C-N bond cleavage method.