Mendip House was built on the west side of Pullen’s Lane by 1900, the first year that it is listed in Kelly’s Directory. Its first occupant was the cricketer Herbert Francis Fox, who was now a tutor at Brasenose College, Oxford. He was away at the time of the 1901 census (boarding by himself at White House Farm in Benhall, East Sussex), but his two young children (Herbert and Rachel) were at Mendip House with two servants. He remained at the house until 1908.

In February 1909 Robert Howard Hodgkin, Fellow & Lecturer in Modern History at The Queen’s College, Oxford, moved in with his wife. They were away at the time of the 1911 census and the house was occupied by two servants. (Their son Thomas Lionel Hodgkin who was born at the house on 3 April 1910 also became a prominent historian, and his wife Dorothy Hodgkin was the Nobel prize-winning chemist.) The Hodgkins lived there until 1918.

From 1918 to 1956 Mendip House was occupied by Joseph Hume Hume-Rothery (b. 1866), a barrister and patents lawyer from Cheltenham, and his wife, Ellen Maria Carter. Their son William came up to Magdalen College, Oxford in the same year that the family moved from Cheltenham to Headington, and they may have come here partly to support him, as he had gone completely deaf in 1916 as a result of meningitis. (William Hume-Rothery later achieved fame as a chemist and mineralogist and lived in Sandfield Road, Headington.)

The house appears to have been empty in 1958.

From 1960 it was occupied by Dr H. D. Leggatt. In 1972 he built a new house below Mendip House called Brock Leys, and sold Mendip House to Dr Kenworthy Browne, who extended Mendip House to the west.

In 1985 Mendip House was sold and the western extension was then split off from the main house to form two separate flats. It was sold again in 1986 with the flats forming a separate freehold from the main house. A summer room was added to the south in 2005 and a garage to the north in 2012.