Word acquisition could be mediated by the neurocognitive mechanism known as fast mapping (FM). It refers to a process of incidental exclusion-based learning and is believed to be a critical mechanism for the rapid build-up of lexicon, although its neural mechanisms are still poorly understood. To investigate the neural bases of this key learning skill, we used event-related potentials (ERPs) and employed an audio-visual paradigm that included a counterbalanced set of familiar and novel spoken word forms presented, in a single exposure, in conjunction with novel and familiar images. To define learning-related brain dynamics, passive auditory ERPs, known to index long-term memory trace activation, were recorded before and after the FM task. Following the single FM learning exposure, we found a significant enhancement in neural activation elicited by the newly trained word form, which was expressed at ~200–400 ms after the word onset. No similar amplitude increase was found either for the native familiar word used as a control stimulus in the same learning paradigm or for similar control stimuli which were not subject to training. Topographic analysis suggested a left-lateral shift of the ERP scalp distribution for the novel FM word form, underpinned by fronto-temporal cortical sources, which may indicate the involvement of pre-existing neurolinguistic networks for mastering new word forms with native phonology. Overall, the near-instant changes in neural activity after a single-shot novel word training indicate that FM could promote rapid integration of newly learned items into the brain’s neural lexicon, even in adulthood.