The railway line is operated by two companies: Società Subalpina di Imprese Ferroviarie (I) and Ferrovie e autolinee regionali ticinesi (CH).

Società Subalpina di Imprese Ferroviarie (SSIF) is a private joint-stock company. Since 1912, it has been the licence holder for the construction and operation of the international one-metre electrified narrow-gauge track from Domodossola up to the Swiss border.

Ferrovie e autolinee regionali ticinesi is a public transport company in the Locarno region and has operated the Swiss part of the railway from Locarno to the Swiss border since 1923. Ferrovie Autolinee Regionali Ticinesi is a joint-stock company entered in the Ticino commercial register with capital in registered shares (public corporations) and bearer shares (private individuals). In addition to the Ferrovia delle Centovalli (federal licence since 1905), the Locarno company also operates the bus lines for the town network of Locarno (3 lines) and the region (5 lines) as well as the Verdasio–Rasa and Intragna–Pila–Costa cableways.