[7] The Cossonay–Bussigny-près-Lausanne section was opened in 1855 by the Compagnie de l'Ouest-Suisse (West Switzerland Company, OS) as part of the construction of the Jura Foot Railway.

[9] A cross-border connection to the French rail network was opened in 1875 with the completion of the tunnel under the Col de Jougne.

However, the trains from France to Switzerland had to make a zig zag turn until 1915, when the opening of the Mont d’Or Tunnel and the new line to Frasne created a direct route.

[10] The line was completed by the OS, the Compagnie de la Ligne d'Italie ("Company of the Italian line") and the Compagnie du chemin de fer du Simplon ("Simplon Railway Company") in subsequent stages, ending with the closing of the Leuk–Brig gap in 1878.

The Simplon tunnel was electrified with 3000 Volt 16 Hertz three-phase AC power from the beginning of operations until 1930.

The dispatcher at the nearby Italian south ramp (Iselle–Domodossola) has worked under Swiss regulations since the establishment of the SBB.

[11] The section, which is equipped with the Swiss train protection system belongs to Ferrovie dello Stato (FS), which also provides the ground personnel.

Even in the 21st century, with open access, the majority of traffic on the Italian section is hauled by Swiss locomotives.

Since the closure of the Trans Europ Express service from Paris to Milan, only nightly passenger trains have run the full distance.

Between Vallorbe and Lausanne long-distance TGV services run to/from Paris, which are extended in the winter season to Brig.

Between Cossonay and Bussigny or Lausanne the route is still operated by ICN trains, which run over the Jura Foot Railway.

Between the stations of La Sarraz and Cossonay, the Jura Foot Railway from Olten connects with the line.

The MGB runs from Brig, where the Lötschberg Mountain Railway connects with the Simplon line towards the Upper Valais.

After Brig, the line runs into the Simplon Tunnel, in the middle of which is the national border between Switzerland and Italy.