Background: Amnestic mild cognitive impairment (aMCI) has a high conversion risk to Alzheimer's disease (AD). The aMCI patients may have only a memory deficit (single-domain-aMCI, sd-aMCI) or deficits in multiple cognitive domains (multiple-domain-aMCI, md-aMCI). However, differences in intrinsic brain activity between these two sub-types remain unclear. Method: Neuropsychological and resting-state functional magnetic resonance imaging (fMRI) data were acquired from 24 patients with sd-aMCI, 23 patients with md-aMCI, and 32 healthy controls (HCs). We used the fractional amplitude of low-frequency fluctuation (fALFF) to characterize the intensity of spontaneous brain activity. The analysis of covariance (ANCOVA) and post hoc tests was performed to determine the between-group differences in fALFF. Results: We found higher fALFF in left-sided superior-to-middle frontal gyri and middle-to-inferior temporal gyri in sd-aMCI compared to both the md-aMCI and HCs. Conversely, a lower fALFF was found in the left inferior parietal lobe in both the md-aMCI and sd-aMCI patients. The fALFF values in the left middle and inferior temporal gyri were correlated with cognitive performances. Conclusion: The gradual reduction in the left inferior parietal lobe from single to multiple domain aMCI suggest a functional inefficiency underlying cognitive impairment, while increased activity in the frontal and temporal gyri in sd-aMCI rather than md-aMCI might indicate functional compensation. This study indicates differential functional profiles in the sd-aMCI and md-aMCI, which may be helpful for the prediction of the future conversion of aMCI to AD. Copyright © 2020 Zhou, Wang, Zhang, Wang and Liu.