The line connects Milan and Domodossola with Brig, an important Swiss railway junction, via the Simplon Tunnel.

Direct passenger trains ran from Brig to Paris (via Lausanne and Geneva ) and Brussels and Luxembourg via Basel.

The line runs through lower Varese Province, the valley of Ossola and along the shore of Lake Maggiore.

[1] It was part of the Società per le strade ferrate dell'Alta Italia (Upper Italian Railways) from 1865, the Società per le Strade Ferrate del Mediterraneo (Mediterranean Railway Company) from 1885 and Ferrovie dello Stato from 1905.

After Baveno, it enters the Toce plain and runs for about 30 km (19 mi) up the Ossola valley to Domodossola.