Route 72 was first allocated to the line between Camberwell (Burke Road) and the City (Swanston Street) on 1 November 1970.

Due to congestion during peak hours at the crossover, some trams continued north to Melbourne University.

The section of track between Queensberry Street (Stop 4) and Commercial Road (Stop 25) is the oldest section of this route, dating back to the Brighton Road cable tram which opened on 11 October 1888 by the Melbourne Tramway & Omnibus Company.

This cable tram line was electrified in stages by the Melbourne & Metropolitan Tramways Board.

[5] In response to the State Government's Melbourne 2030 planning policy, the Public Transport Users Association lobbied to extend route 72 north to Doncaster Road and Ivanhoe station, and south to Caulfield.