Transamidation reactions are often mediated by reactive substrates in the presence of overstoichiometric activating reagents and/or transition metal catalysts. Here we report the use of CO2 as a traceless catalyst: in the presence of catalytic amounts of CO2, transamidation reactions were accelerated with primary, secondary, and tertiary amide donors. Various amine nucleophiles including amino acid derivatives were tolerated, showcasing the utility of transamidation in peptide modification and polymer degradation (e.g., Nylon-6,6). In particular, N,O-dimethylhydroxyl amides (Weinreb amides) displayed a distinct reactivity in the CO2-catalyzed transamidation versus a N2 atmosphere. Comparative Hammett studies and kinetic analysis were conducted to elucidate the catalytic activation mechanism of molecular CO2, which was supported by DFT calculations. We attributed the positive effect of CO2 in the transamidation reaction to the stabilization of tetrahedral intermediates by covalent binding to the electrophilic CO2.