Background: Amyotrophic lateral sclerosis (ALS) is a devastating disease that targets motor neurons. Upper motor neurons degeneration is pathologically characterized by brain iron accumulation. Signal attenuation in the shape of a ribbon at the posterior border of the precentral gyrus can be observed on conventional magnetic resonance imaging (MRI) sequences including T2-weighted sequence. Methods: With the aim to know the qualities of this potential marker of ALS, we conducted a prospective study. Patients with definite ALS in the age range of 40–70 years and healthy controls underwent 3T brain MRI using a standardized sequence. A second MRI was performed 18 months later under the same conditions in the patients with ALS. Results: Most of the patients with ALS (91.66%) exhibited a “black ribbon” (BR) with an average area of 79.98 mm3. Signal attenuation discriminated ALS with a mean value of 63.97 arbitrary units (AU) on the left BR (95% CI: 60.67–67.27), a mean value of 59.15 AU (95% CI: 54.78–63.53) on the right BR, and a significant difference with control subjects presenting a mean value of 107.85 AU (p < 0.001). The optimal cut-off point for differentiating patients with ALS from controls (sensitivity, 0.92; specificity, 0.93) was 83 AU. Forced vital capacity and muscle strength in the contralateral upper extremity were significantly correlated with the ribbon intensity in ALS. Patients who underwent a second study exhibited significant changes in the BR related to the rapid evolution of the disease. Conclusions: This marker represents a valuable tool for the selection of candidates and their follow-up in clinical trials.