Paralysis occurring in amyotrophic lateral sclerosis (ALS) leads to denervation of skeletal muscle as a consequence of motor neuron degeneration. The spatiotemporal ordering of events that drive these processes in whole spinal tissues remains poorly understood, although interactions between glia and motor neurons contribute to motor neuron loss. Here, we utilize transcriptomics to acquire gene expression measurements of mouse spinal cords from ALS patients, and also of postmortem tissue over the course of disease, to describe the molecular mechanisms in ALS. We discern perturbations in many transcriptional pathways shared between murine models of human spinal cords and ALS, differentiate differences between microglia and astrocyte populations and identify dynamics.