Jackson was born at Green Hammerton in England and educated at York Hospital and St. Bartholomew's Hospital, London. He received his MD from St. Andrews University in 1860. He served on the staff of the London Hospital as assistant physician (1863) and physician (1874–94) and in 1862 began his long association with the National Hospital for the Paralysed and Epileptic, London. Here he specialized in neurology and ultimately exercised a profound influence on the development of clinical neurology. Through his work with epileptics, he described the condition, now called Jacksonian seizure or Jacksonian epilepsy, in which part of the leg, arm, or face undergoes spasmodic contraction due to local disease of the cerebral cortex in the brain.

Jackson's work supported the findings of Paul Broca and others – that different bodily functions are controlled by different regions of the cerebral cortex. Jackson also described a local paralysis of the tongue and throat caused by disease of the corresponding cranial nerves. This is now known as Jackson's syndrome.