AbstractObjectiveSpinal cord degeneration is a hallmark of amyotrophic lateral sclerosis. The assessment of gray matter and white matter cervical spinal cord atrophy across clinical stages defined using the King's staging system could advance the understanding of amyotrophic lateral sclerosis progression.MethodsWe assessed the in vivo spatial pattern of gray and white matter atrophy along cervical spinal cord (C2 to C6 segments) using 2D phase‐sensitive inversion recovery imaging in a cohort of 44 amyotrophic lateral sclerosis patients, evaluating its change across the King's stages and the correlation with disability scored by the amyotrophic lateral sclerosis functional rating scale revised (ALSFRS‐R) and disease duration. A mathematical model inferring the potential onset of cervical gray matter atrophy was developed.ResultsIn amyotrophic lateral sclerosis patients at King's stage 1, significant cervical spinal cord alterations were mainly identified in gray matter, whereas they involved both gray and white matter in patients at King's stage ≥ 2. Gray and white matter areas correlated with clinical disability at all cervical segments. C3–C4 level was the segment showing early gray matter atrophy starting about 7 to 20 months before symptom onset according to our model.InterpretationOur findings suggest that cervical spinal cord atrophy spreads from gray to white matter across King's stages in amyotrophic lateral sclerosis, making spinal cord magnetic resonance imaging an in vivo assessment tool to measure the progression of the disease.