The original municipality of Knox was established in 1963 by severance from the Shire of Ferntree Gully, which had been formed in 1889. The Shire of Ferntree Gully comprised both Knox and most of the former Shire of Sherbrooke. Prior to 1889, the area covered by the Shire of Ferntree Gully had been part of the Shire of Berwick and was known as the Scoresby Riding.
On 16 November 1963, the original municipality of Knox was established with an area of 110 square kilometres and a population of 24,000 people.
Knox was proclaimed a City on 4 July 1969, and by then had a population of 50,000 people.
On 15 December 1994, following a review of local government, a new City of Knox was proclaimed. As part of this amalgamation process, sections of Upper Ferntree Gully and Lysterfield became a part of the new City of Knox. Knox comprises 11 suburbs: Bayswater, Boronia, Ferntree Gully, Lysterfield, Knoxfield, Rowville, Scoresby, The Basin, Upper Ferntree Gully, Wantirna, and Wantirna South.
The population figure for the City of Knox is now in excess of 150,000, approximately 58,000 homes, and covers an area of 113.84 square kilometres. There are a total of 14,000 businesses in Knox, including 5,000 home-based businesses.