The railway station was inaugurated on December 4, 1882. It marked a significant turning point for the small town of Luino, which suddenly became a center of international trade. The passage of goods, tourists, and workers spurred a rapid urban and social transformation.
Due to its proximity to the border, the station was chosen as the location for an international customs office. Its historical importance is easily understood just by considering its large spaces: the original complex included 19 buildings. The most prestigious space was the customs hall, with its marble floor allowing direct access to the platforms. There were barracks, warehouses, waiting rooms, and even an elegant restaurant.
Several decorative elements were inspired by Milano Centrale railway station, such as iron-and-glass partitions, columns, blind windows, frontons, and, at the top of the structure, a large double-faced clock (later replaced). The station also featured a spacious iron-and-glass platform roof, which was dismantled in 1941.
The locomotive hangar, built on the occasion of the opening of the Gotthard Base Tunnel (1882), now houses the Verbano Railway Museum.

…la facciata troneggiava sopra la piazza appena abbozzata, i fasci dei binari luccicavano da via Voldomino al ponte di Germignaga, l’enorme tettoia, simile a quella della Gare de Lyon a Parigi, accoglieva le prime fumate delle locomotive. Fiori, bandiere, gli ottoni delle bande, autorità, belle signore e un po’ di popolo riempivano gli atri e i marciapiedi.
Andare alla stazione voleva dire uscire dal paese per entrare in un ambiente favoloso, popolato di stranieri in transito, di mercanti, spedizionieri, guardie di finanza, carabinieri, ferrovieri svizzeri e italiani in divisa, agenti di pubblica sicurezza.

Piero Chiara, Una stazione immaginaria, 1982

The international railway station and the customs office attracted entrepreneurs and workers to Luino from every region of Italy as well as from nearby Switzerland. Among them was also the father of Vittorio Sereni, Enrico Sereni, originally from Sant’Agata de’ Goti (though of Venetian descent), who arrived in Luino as a customs officer. There he met Maria Michelina Colombi, a member of a wealthy family from Luino. Their son, Vittorio Sereni, was born on 27 July 1913.