Understanding the relevant meaning of a word with different meanings (homonym) in a given context requires activation of the neural representations of the relevant meaning and inhibition of the irrelevant meaning. The cognitive demand of such disambiguation is highest when the dominant, yet contextually irrelevant meaning of a polar homonym must be suppressed. This central process (semantic inhibition) for lexico-semantic ambiguity resolution was monitored with fMRI during semantic context verifications. Twenty-two healthy volunteers decided whether congruent or incongruent target words fitted into the contexts established by preceding sentences. Half of the sentences ended with a homonym, thereby allowing to cross the factors ambiguity and semantic congruency. BOLD increases related to the inhibitory attentional control over non-selected meanings during ambiguity processing occurred in a brain network including left dorsolateral prefrontal cortex (DLPFC), bilateral angular gyrus (AG), bilateral anterior superior temporal gyrus (aSTG) as well as right ventromedial temporal lobe. In left DLPFC (BA 46/9) and left AG (BA 39) BOLD activity to target words of the incongruent-ambiguous condition correlated with the individual amount of semantic interference experienced by the subjects. BOLD increases of incongruent versus congruent semantic verifications occurred in bilateral inferior frontal gyrus. The results of the present study suggest a specific role of left DLPFC and AG in the resolution of semantic interference from contextually inappropriate homonym meanings. These fronto-parietal areas might exert inhibitory control over temporal regions in service of attentional selection between relevant and irrelevant homonym meanings, by creating a sufficient activation difference between their respective representations.