He was the first Linacre Professor of Anatomy and Physiology to be appointed at the University of Oxford, a post he held from 1860 until his death in 1881.

In 1860, he was elected to the newly founded Linacre Professorship of Anatomy and Physiology, which he held to the time of his death.

He had gone to Italy and France to seek treatment but returned to England a week prior to his death after his condition did not improve and finding out that Grace was seriously ill.[4] In Who Do You Think You Are?, his great-grandson Frank Gardner, while researching on why his grandfather John Rolleston (George's son) was so reticent about his childhood, discovered that Grace suffered from a mental breakdown after her husband's death and was committed to Warneford and Chiswick asylums and that a thirteen-year-old John had witnessed one of his mother's breakdowns.

[5] As a zoologist, Rolleston was a protégé of Thomas Henry Huxley, and took part in both of the critical sessions at the 1860 British Association meeting in Oxford.

Huxley was instrumental in Rolleston's appointment to the Linacre chair that very year, backing him against Owen's candidate.

Rolleston was an Anglican, but a liberal in his religious beliefs, as was Huxley's other supporter in the brain debate, William Henry Flower.

Huxley organised his FRS, as he did for Flower; and the two men acted as liaison between the X-Club and the Royal Society.