A time-resolved kinetic study in acetonitrile and a theoretical investigation of hydrogen abstraction reactions from N,N-dimethylformamide (DMF) and N,N-dimethylacetamide (DMA) by the cumyloxyl (CumO•) and benzyloxyl (BnO•) radicals was carried out. CumO• reacts with both substrates by direct hydrogen abstraction. With DMF, abstraction occurs from the formyl and N-methyl C–H bonds, with the formyl being the preferred abstraction site, as indicated by the measured k H/k D ratios and by theory. With DMA, abstraction preferentially occurs from the N-methyl groups, whereas abstraction from the acetyl group represents a minor pathway, in line with the computed C–H BDEs and the k H/k D ratios. The reactions of BnO• with both substrates were best described by the rate-limiting formation of hydrogen-bonded prereaction complexes between the BnO• α-C–H and the amide oxygen, followed by intramolecular hydrogen abstraction. This mechanism is consistent with the very large increases in reactivity measured on going from CumO• to BnO• and with the observation of k H/k D ratios close to unity in the reactions of BnO•. Our modeling supports the different mechanisms proposed for the reactions of CumO• and BnO• and the importance of specific substrate/radical hydrogen bond interactions, moreover providing information on the hydrogen abstraction selectivity.