The station is managed by Rete Ferroviaria Italiana (RFI), the commercial area of the passenger building by Centostazioni, while train services on the line to Novara are operated by Trenitalia.

These two lines combine to form an international link, via Domodossola, between the German and Italian speaking parts of Switzerland.

Domodossola railway station is situated at Piazza Giacomo Matteotti, at the eastern edge of the city centre.

On 1 June 1906, Domodossola was extended to become an international facility, upon the opening of the Simplon Tunnel and the Brig–Domodossola railway that passes through it.

[2] From the bus terminal located near the station there are direct buses to the main municipalities in the Ossola valley, and inter-urban routes to Verbania, Omegna and Milan Malpensa Airport.