Determining atomic-level characteristics of molecules on two-dimensional surfaces is one of the fundamental challenges in chemistry. High-resolution nuclear magnetic resonance (NMR) could deliver rich structural information, but its application to two-dimensional materials has been prevented by intrinsically low sensitivity. Here we obtain high-resolution one-and two-dimensional P-31 NMR spectra from as little as 160 picomoles of oligonucleotide functionalities deposited onto silicate glass and sapphire wafers. This is enabled by a factor >10(5) improvement in sensitivity compared to typical NMR approaches from combining dynamic nuclear polarization methods, multiple-echo acquisition, and optimized sample formulation. We demonstrate that, with this ultrahigh NMR sensitivity, P-31 NMR can be used to observe DNA bound to miRNA, to sense conformational changes due to ion binding, and to follow photochemical degradation reactions.