High‐resolution mass spectrometry (HRMS) imaging by desorption electrospray ionization (DESI) coupled with Orbitrap MS using methanol (MeOH) spray was performed on a fragment of the Murchison (CM2) meteorite in this study. Homologues of CnH2n–1N2+ (n = 7–9) and CnH2nNO+ (n = 9–14) were detected on the sample surface by the imaging. A high‐performance liquid chromatography (HPLC)/HRMS analysis of MeOH extracts from the sample surface after DESI/HRMS imaging indicated that the CnH2n–1N2+ homologues corresponds to alkylimidazole, and that a few isomers of the CnH2nNO+ homologues present in the sample. The alkylimidazoles and CnH2nNO+ homologues displayed different spatial distributions on the surface of the Murchison fragment, indicating chromatographic separation effects during aqueous alteration. Moreover, the distribution pattern of compounds is also different among homologues. This is probably also resulting from the separation of isomers by similar chromatographic effects, or different synthetic pathways. Alkylimidazoles and the CnH2nNO+ homologues are mainly distributed in the matrix region of the Murchison by mineralogical observations, which is consistent with previous reports. Altered minerals (e.g., Fe‐oxide, Fe‐sulfide, and carbonates) occurred in this region. However, no clear relationship was found between these minerals and the organic compounds detected by DESI/HRMS imaging. Although this result might be due to scale differences between the spatial resolution of DESI/HRMS imaging and the grain size in the matrix of the Murchison, our results would indicate that alkylimidazoles and the CnH2nNO+ homologues in the Murchison fragment were mainly synthesized by different processes from hydrothermal alteration on the parent body.