Historically in Lancashire, Chorlton-on-Medlock is bordered to the north by the River Medlock, which runs immediately south of Manchester city centre.

Neighbouring districts are Hulme to the west, Ardwick to the east and Victoria Park, Rusholme and Moss Side to the south.

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[1] 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.

Few dwellings of that period remain today apart from Waterloo Place, 323, 325, 327 & 333 Oxford Road, and Grove House (316–324).

At this time the southern area was still partly rural with some larger dwellings of wealthy people (e.g., John Owens in Nelson Street).

In Greenheys there was formerly an Anglican church of St Clement on Denmark Road (architect Henry R. Price, 1881, decorated by John Lowe, 1886[8]).

St Augustine's, Granby Row (demolished in 1908 to allow expansion at the Municipal College of Technology) was replaced by a second St Augustine's in York Street, Chorlton-on-Medlock (ruined by German bombing in 1940 during World War II):[9] its successor is at Lower Ormond Street on the Manchester Metropolitan University campus in a building which serves also as a chaplaincy to the University.

The chapel in Cavendish Street was a particularly fine neo-Gothic building but was demolished in the early 1970s to allow expansion by Manchester Polytechnic.

It was founded in 1879 and a modern Salvation Army building stands on the site of the original one, and is called Manchester Central.