This study investigates the structure-function relationships between the anatomy of Heschl's gyri (HG) and speech hemispheric lateralization in 281 healthy volunteers (135 left-handers). Hemispheric lateralization indices (HFLIs) were calculated with Wilke's method from the activations obtained via functional magnetic resonance imaging while listening to lists of words (LIST). The mean HFLI during LIST was rightward asymmetrical, and left-handers displayed a trend toward decreased rightward asymmetry. The correlations between LIST BOLD contrast maps and individual HFLIs demonstrated that among the cortical areas showing significant asymmetry during LIST, only phonological regions explained HFLI variability. Significant positive correlations were present among the left HG, supramarginal gyri, and the anterior insula. Significant negative correlations occurred in the mid-part of the right superior temporal sulcus. Left HG had the largest functional activity during LIST and explained 10% of the HFLI variance. There was a strong anatomo-functional link in the HG: duplication was associated with a decrease in both the surface area of the anterior HG and HG functional activity. Participants with a single left HG exhibited leftward anatomical and functional asymmetry of HG, but participants with a left duplication lost either anatomical and/or functional leftward asymmetries. Finally, manual preference was related to HG anatomy, but not to HG functional asymmetries measured during LIST. The anatomical characteristics of left-handers (lower occurrence of right HG duplication and a smaller surface area of the right first HG) thus appeared to be unrelated to variations in speech lateralization with handedness.