Our ability to manipulate and understand the use of a wide range of tools is a feature that sets humans apart from other animals. In right-handers, we previously reported that hearing hand-manipulated tool sounds preferentially activates a left hemisphere network of motor-related brain regions hypothesized to be related to handedness. Using functional magnetic resonance imaging, we compared cortical activation in strongly right-handed versus left-handed listeners categorizing tool sounds relative to animal vocalizations. Here we show that tool sounds preferentially evoke activity predominantly in the hemisphere “opposite” the dominant hand, in specific high-level motor-related and multisensory cortical regions, as determined by a separate task involving pantomiming tool-use gestures. This organization presumably reflects the idea that we typically learn the “meaning” of tool sounds in the context of using them with our dominant hand, such that the networks underlying motor imagery or action schemas may be recruited to facilitate recognition.