It touches the villages of Druogno, Santa Maria Maggiore, Malesco and Intragna and carried over 1 million passengers in 2010.

It is operated by the Ferrovie Autolinee Regionali Ticinesi (FART) in Switzerland and the Società Subalpina Imprese Ferroviarie [de] (SSIF) in Italy.

[2][3] Opened on 25 November 1923, the 52-kilometre (32 mi) long railway has 30 stations and takes approximately 2 hours to traverse the whole length.

Following a convention signed in Rome on 12 November 1918 between the plenipotentiaries Sidney Sonnino and De Segesser, respectively, of the King of Italy and the Federal Council of the Swiss Confederation, the construction of the railway began.

[7] The route, like other mountain railways, has some dramatic inclines between the Masera and Santa Maria Maggiore (Italy), and between Verdasio and Intragna (Switzerland); in some places the gradient is 60 per thousand.

Similarly to the international Brig–Domodossola connection (through the Simplon Tunnel), the entire Domodossola–Locarno line is included in the scope of the various Swiss Rail flat rate and discount passes (excluding supplements), the Brig–Locarno route constituting a shortcut between western Switzerland and Ticino.