Shortly after the opening of the first railway in Switzerland, each region began to favour a separate north–south link through the Alps towards Italy.

The Compagnie de la Ligne d'Italie was founded in 1856 to build a connection between Romandy and Italy through the Canton of Valais and the Simplon.

The company considered 31 proposals and selected one that involved the construction of a tunnel from Glis to Gondo, which would have been fully in Switzerland.

At a Swiss-Italian conference held in July 1889, it was agreed, however, to build a nearly 20-kilometre long (12 mi) base tunnel through the territory of both states.

They were mostly Italians, who suffered under very poor working conditions: 67 workers were killed in accidents; many died later of diseases.

BBC had no electric locomotives and initially acquired three locomotives built for the Ferrovia della Valtellina—the owner of the lines from Colico to Chiavenna and Tirano, which had been electrified with this system in 1901 and 1902[5]—from their owner, the Rete Adriatica (Adriatic Network) railway company.

In Italy, the German army planned, as part of its 1945 withdrawal, to blow up the tunnel, but was thwarted by Italian partisans with the help of two Swiss officials and Austrian deserters.

There is a car-carrying shuttle between Brig and Iselle di Trasquera, which provides a 20-minute train journey as an alternative to driving over the Simplon Pass.

As roads over the Simplon Pass steadily improved throughout the 1970s and 1980s the tunnel's shuttle schedule was cut back, then ended altogether on 3 January 1993.

Later, adjustments were made to the tunnel profile for piggyback traffic; in places only widening one track was possible.

Clearances were also raised for the piggyback traffic on the Italian side as well on the Simplon southern approach.

In November 2004, the 7-kilometre long (4.3 mi) new line between Salgesch and Leuk in the Rhone Valley was completed to replace the last single-track bottleneck on the route.

Under the ZEB ("Future rail development projects") package, the maximum speed on the long straight sections of the Rhone valley lines will be increased from 160 to 200 km/h (99 to 124 mph).

[8] In the 1957 novel From Russia, with Love by Ian Fleming, protagonist James Bond fights his enemy, SMERSH agent Donovan Grant, eventually killing him, while passing through the Simplon Tunnel on the Orient Express.

In Against the Day by Thomas Pynchon, Reef Traverse, one of the novel's characters, works on the construction of the Simplon Tunnel.

[9] In the novel "The Couloir" by Richard Manichello, the Canton Valais is a major geographical setting for action and scenes.

Brig and the Simplon Pass & Tunnel play an important role in the main plot, moving characters in and out of Western Swiss locations or over the Pennine Alps for various intrigues and subplots involving action that traverses Swiss and Italian story settings.