The ability to self-regulate can become impaired when people are required to engage in successive acts of effortful self-control, even when self-control occurs in different domains. Here, we used functional neuroimaging to test whether engaging in effortful inhibition in the cognitive domain would lead to putative dysfunction in the emotional domain. Forty-eight participants viewed images of emotional scenes during functional magnetic resonance imaging in two sessions that were separated by a challenging attention control task that required effortful inhibition (depletion group) or not (control group). Compared to the control group, depleted participants showed increased activity in the left amygdala to negative but not to positive or neutral scenes. Moreover, whereas the control group showed reduced amygdala activity to all scene types (i.e. habituation), the depletion group showed increased amygdala activity relative to their pre-depletion baseline; however this was only significant for negative scenes. Finally, depleted participants showed reduced functional connectivity between the left amygdala and ventromedial prefrontal cortex during negative scene processing. These findings demonstrate that consuming self-regulatory resources leads to an exaggerated neural response to emotional material that appears specific to negatively valenced stimuli and further suggests a failure to recruit top-down prefrontal regions involved in emotion regulation.