Chorlton-on-Medlock is an inner city area of Manchester, England.

Historically in Lancashire, Chorlton-on-Medlock is bordered to the north by the River Medlock, which runs immediately south of Manchester city centre. Its other borders roughly correspond to Stockport Road, Hathersage Road, Moss Lane East and Boundary Lane. Neighbouring districts are Hulme to the west, Ardwick to the east and Victoria Park, Rusholme and Moss Side to the south. A large portion of the district along Oxford Road is occupied by the campuses of the University of Manchester, Manchester Metropolitan University, and the Royal Northern College of Music. To the south of the university's Oxford Road campus a considerable area is occupied by a group of contiguous hospitals including Manchester Royal Infirmary, to the west of which is Whitworth Park.

In medieval times, the district was known as Chorlton Row and was a township of the ancient parish of Manchester in the Salford hundred of Lancashire. Towards the end of the 18th century, it developed as a residential suburb of Manchester and in the extreme north of the township a number of cotton mills were established. In 1820 the parish church of All Saints was built. Development began in 1793–94 and most of the important streets were given impressive names, Oxford Street, Cambridge Street and Grosvenor Street.

Over the following 30 years residential development spread southwards as far as Tuer Street: and by the mid-1840s to High Street. Few dwellings of that period remain today apart from Waterloo Place, 323, 325, 327 & 333 Oxford Road, and Grove House (316–324).

On the creation of the municipal borough of Manchester in 1838 the township was absorbed into the borough. At this time the southern area was still partly rural with some larger dwellings of wealthy people (e.g., John Owens in Nelson Street). After the Poor Law Reform of 1834 the district became part of the Chorlton Poor Law Union and the offices of the Board of Guardians were built in Cavendish Street (these are now the Ormond Building of the Metropolitan University). The arrival of Owens College in 1873 was the beginning of a different kind of development leading to the academic campus of today.

In 1866 Chorlton upon Medlock became a separate civil parish, on 26 March 1896 the parish was abolished to form South Manchester. In 1891 the parish had a population of 59,620.

Though most of the township was originally middle class in character by the early 20th century it was very much a working class district. The housing conditions were described in 1931 by the Manchester and District Social Survey Society.

Between the arrival of Owens College in 1873 and the 1940s the college and the university it became slowly expanded into the adjacent residential areas which had by then a mostly working class population including many of Irish descent. However, during the early years of the 21st century the University of Manchester undertook an extensive Capital Development Project which was followed by a partnership with the city council and other bodies called Corridor Manchester. Together these have changed the face of Oxford Road to a remarkable extent.