We investigated the impact of contextual constraint on the integration of novel word meanings into semantic memory. Adults read strongly or weakly constraining sentences ending in known or unknown (novel) words as scalp-recorded electrical brain activity was recorded. Word knowledge was assessed via a lexical decision task in which recently seen known and unknown word sentence endings served as primes for semantically related, unrelated, and synonym/identical target words. As expected, N400 amplitudes to target words preceded by known word primes were reduced by prime-target relatedness. Critically, N400 amplitudes to targets preceded by novel primes also varied with prime-target relatedness, but only when they had initially appeared in highly constraining sentences. This demonstrates for the first time that fast-mapped word representations can develop strong associations with semantically related word meanings and reveals a rapid neural process that can integrate information about word meanings into the mental lexicon of young adults.