(1) Background: Alzheimer's disease (AD) is a neurodegenerative disease with a high prevalence. Despite the cognitive tests to diagnose AD, there are pitfalls in early diagnosis. Brain deposition of pathological markers of AD can affect the direction and intensity of the signaling. The study of effective connectivity allows the evaluation of intensity flow and signaling pathways in functional regions, even in the early stage, known as amnestic mild cognitive impairment (aMCI). (2) Methods: 16 aMCI, 13 AD, and 14 normal subjects were scanned using resting-state fMRI and T1-weighted protocols. After data pre-processing, the signal of the predefined nodes was extracted, and spectral dynamic causal modeling analysis (spDCM) was constructed. Afterward, the mean and standard deviation of the Jacobin matrix of each subject describing effective connectivity was calculated and compared. (3) Results: The maps of effective connectivity in the brain networks of the three groups were different, and the direction and strength of the causal effect with the progression of the disease showed substantial changes. (4) Conclusions: Impaired information flow in the resting-state networks of the aMCI and AD groups was found versus normal groups. Effective connectivity can serve as a potential marker of Alzheimer's pathophysiology, even in the early stages of the disease.