It opened to goods traffic (mainly coal and iron) in September 1865 and to passengers in August 1866.

Stations in the first service on the line were at Carmyle, Broomhouse (now Mount Vernon), Baillieston, Langloan and Whifflet High Level (until 1964).

Passenger services ceased in November 1966 following the Beeching Axe (latterly running to Coatbridge Central).

As part of the improvement works, engineers completed a series of projects to repair and replace infrastructure on the line through central Glasgow.

The line between Rutherglen and Exhibition Centre was closed throughout the works, and no trains ran.

In 2006, Network Rail announced tentative proposals to electrify the Rutherglen - Whifflet section as part of a £1.4bn upgrade to Scotland's railways.