Willis worked as a physician in Westminster, London, and from 1660 until his death was Sedleian Professor of Natural Philosophy at Oxford. He was a pioneer in research into the anatomy of the brain, nervous system and muscles. The "circle of Willis", a part of the brain, was his discovery.
His anatomy of the brain and nerves, as described in his Cerebri anatomi of 1664, is so minute and elaborate, and abounds so much in new information, that it presents an enormous contrast with the vague and meagre efforts of his predecessors. This work was not the result of his own personal and unaided exertions; he acknowledged his debt to Sir Christopher Wren and Thomas Millington, and his fellow-anatomist Richard Lower.
Willis was the first to number the cranial nerves in the order in which they are now usually enumerated by anatomists. His observation of the connexion of the eighth pair with the slender nerve which issues from the beginning of the spinal cord is known to all. He remarked the parallel lines of the mesolobe, afterwards minutely described by Felix Vicq d'Azyr. He seems to have recognized the communication of the convoluted surface of the brain and that between the lateral cavities beneath the fornix. He described the corpora striata and optic thalami; the four orbicular eminences, with the bridge, which he first named annular protuberance; and the white mammillary eminences, behind the infundibulum. In the cerebellum he remarks the arborescent arrangement of the white and grey matter, and gives a good account of the internal carotids, and the communications which they make with the branches of the basilar artery.