The ventromedial prefrontal cortex's (vMPFC) role in regulating emotions in late life depression (LLD) remains unclarified. We assessed vMPFC activation in an emotional valence blood oxygenation level-dependent (BOLD) functional magnetic neuroimaging (fMRI) task and related the findings to extent of white matter hyperintensities (WMH). Sixteen participants with mild to moderate LLD were compared to 14 similar aged comparison participants. Participants in the scanner viewed words matched for length and arousal, indicated the perceived valence by pressing one of the three buttons i.e. “positive, negative, or neutral.” WMH volume was greater in LLD participants than comparison participants. There were no differences in activations between groups to any valence contrast. Female LLD participants showed greater activation for negative versus positive and negative versus neutral words as compared to female comparison participants. Female LLD participants respond differently to emotionally laden words compared to comparison participants. WMH could play a role in etiopathology of emotional perception in female LLD participants.