The spinal cord carries motor nerve fibers to the limbs and trunk and sensory fibers from the body back to the brain. Inflammation within the spinal cord interrupts these pathways and causes the common presenting symptoms. TM generally presents with rapidly progressing muscle weakness or paralysis, beginning with the legs and potentially moving to the arms with varying degrees of severity. The arms are involved in a minority of cases and this is dependent upon the level of spinal cord involvement. Sensation is diminished below the level of spinal cord involvement in the majority of individuals. Pain (ascertained as appreciation of pinprick by the neurologist) and temperature sensation are generally diminished and appreciation of vibration (as caused by a tuning fork) and joint position sense may also be decreased. Many report a tight banding or girdle-like sensation around the trunk and that area may be very sensitive to touch.

In most cases a sensory level is documented, most commonly in the mid-thoracic region in adults or the cervical region in children. Pain in the back, extremities, or abdomen is also common while paresthesias (e.g., tingling, numbness, burning sensations) are typical in adults. Sexual dysfunction is also the result of sensory and autonomic involvement. Increased urinary urgency, bowel or bladder incontinence, difficulty or inability to void, and incomplete evacuation of bowel or constipation are other characteristic autonomic symptoms. Spasticity and fatigue are other symptoms common to transverse myelitis. Additionally, depression is often documented in TM patients and must be treated to prevent devastating consequences.

In some cases, symptoms progress over hours whereas in other instances, the presentation is over days. Neurologic function tends to decline during the 4-21 day acute phase, while eighty-percent of cases reach their maximal deficit within 10 days of symptom onset. At its worst point, 50% of individuals have lost all movements of their legs, 80-94% experience numbness, paresthesias or banding or girdling, and almost all have some degree of bladder dysfunction.