DNA is constantly under attack from exogenous and endogenous sources that modify the chemical structure of the nucleobases. A common type of nucleobase damage is N-methylation, which can result in mutagenesis. Nevertheless, these lesions are often repaired by the DNA repair enzyme AlkB, albeit at varying rates. Herein we use density functional theory (B3LYP -D3(BJ)/6-311++G(2df,2p)//B3LYP/6-31G (d,p)) to comprehensively examine the structural and energetic properties of base pairs between seven nucleobase lesions resulting from N-methylation on the Watson-Crick (WC) binding face and each canonical nudeobase. By characterizing 105 stable nucleobase dimers, we provide fundamental details regarding the preferred lesion base pairings. Specifically, we reveal that the flexibility of the methylamino group resulting from methylation of an exocyclic amino substituent allows the 2MeG, 4MeC, and 6MeA lesions to maintain a preference for canonical WC base pairing, which correlates with the experimentally reported lack of mutagenicity for these damage products. In contrast, calculated distortions in key structural parameters and altered binding energies for base pairs involving adducts formed upon methylation of a ring nitrogen (namely, 1MeG, 3MeT, 1MeA, and 3MeC) help rationalize the associated mutagenicity and repair efficiencies. Most importantly, our work provides molecular-level information about the interactions between N-methylated and canonical nudeobases that is critical for future large-scale modeling of damaged DNA and enzyme-DNA complexes that strive to further uncover the mutagenicity and repair propensities of these detrimental lesions.