The classic symptoms of acute ON consist of unilateral loss of vision (in 70 percent of individuals), periocular pain, and dyschromatopsia (color blindness or color vision deficiency). This typically comes on over the course of a few days and peaks within one to two weeks. ON usually begins with decreased vision in one eye. Approximately 90 percent of diagnosed individuals also experience pain behind the eye which is usually exacerbated by eye movement. Visual loss can vary from mild reduction and minor blurring to no perception of light. Symptoms tend to exacerbate with increased body temperature. Other common signs and symptoms of acute ON include visual field defects, swelling of the optic nerve, photopsias (the presence of perceived flashes of light), and an afferent pupillary defect always occurs in ON if the other eye is uninvolved.

Another key aspect of ON is that vision and eye pain usually improve within 2 to 3 weeks after the onset of symptoms. More than 90 percent of individuals experience visual improvement within this timeframe regardless of treatment. Should symptoms persist for longer than 3 weeks, it suggests that it is either an atypical type of ON or is a different diagnosis.