The NBOMe family is a group of new psychoactive substances (NPSs). In this study, the fragmentation patterns of NBOMe derivatives were analyzed using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). The MS/MS spectral data was used to establish a molecular networking map for NBOMe derivatives. The fragmentation patterns of nine NBOMe derivatives were interpreted on the basis of their product ion spectral data. NBOMe derivatives generally showed similar product ion spectral patterns; among them, the halogen-substituted methoxybenzyl ethanamine type derivatives showed a characteristic product ion of a radical cation. Molecular network analysis of the MS/MS data revealed that all NBOMe derivatives formed one integrated networking cluster that discriminated them from other types of NPSs. NBOMe derivatives were spiked into human urine and identified by connection to the NBOMe database network. Furthermore, the NBOMe compounds that were not registered in the database were also recognized as an NBOMe-related substance by molecular networking. These results demonstrate the potential of using molecular networking-based screening methods for designer drugs, and the proposed method would be useful in forensic or doping analysis.