The line runs between the border town of Tocumwal in New South Wales to Southern Cross station in Melbourne.

A line was built from Mangalore to Toolamba and Shepparton in 1880 and extended to Numurkah in 1881, Strathmerton in 1905 and connecting with the New South Wales Government Railways at Tocumwal at a break-of-gauge in 1908.

[1] The last passenger service from Toolamba station to Echuca ran on 2 March 1981 with Y class diesel locomotive Y161, an ABE carriage and a C van.

[2] The passenger service from Numurkah north to Cobram was withdrawn on 24 April 1981 but was restored on 14 August 1983.

[4] On 20 February 2020, a NSW TrainLink XPT passenger train on the adjacent North East railway line towards Sydney derailed at Wallan, resulting in suspension of freight, V/Line and NSW TrainLink services on the North East and Tocumwal railway lines.

On 31 October 2022, after a week long delay due to extensive major flooding in the Goulburn Valley region, VLocity trains started running from Seymour-Shepparton for the first time, replacing the previous N and H set locomotive hauled services.

In addition to these, Pacific National also operates a thrice weekly container service from Tocumwal to Appleton Dock.

[citation needed] In October 1889, the Upfield railway line was extended to Somerton, but closed in July 1903.

A branch line was opened during the Second World War to Broadstore, designed to connect Broadmeadows station with the Maygar Barracks.