Borders of Chorlton-on-Medlock are Stockport road, Moss Lane East, Boundary Lane and Hathersage Road. The northern border of Chorlton-on-Medlock is met by the River Medlock which runs through the south border of Manchester city centre. The University of Manchester, the Royal Northern College of Music and Manchester Metropolitan University all occupy buildings in the area along and around Oxford Road.

Areas which neighbour Chorlton-on-Medlock are Hulme, Ardwick, Victoria Park, Rusholme and Moss Side.