In order to cross of the Apennines the 3,259-metre-long (10,692 ft) Giovi Tunnel was built, which at the time was the longest in the world.

The first leg, only 13 kilometres (8.1 mi) long from Torino Porta Nuova (which had not yet been built) to Trofarello, was opened on 24 September 1848[6] with a simple ceremony.

Regular public service began the next day with six pairs of trains traveling between 7 am and 7 pm.

Already this section required the building of the first important work with a long bridge over the Po River next to the Moncalieri station.

The rail service proved to be satisfactory to the public, with the train taking only 3 hours and 40 minutes to cover the whole route, leading to improved profits for the company.

The 18-kilometre (11 mi) extension to Busalla was opened on 10 February 1853[6] and required the building of eight bridges and four tunnels of lengths varying from 508 to 866 metres (1,667 to 2,841 ft).

On 18 December 1853 the line was completed with the opening of the last 23 kilometres (14 mi) between Busalla and Genova Piazza Principe station.

[10] The new line was needed to meet the significant increase in demand for freight transport to and from the port of Genoa.

At that time steam locomotives were fired with cheap coal briquettes produced by a mixture of pitch, tar and coal dust, which gave off poisonous fumes and forced train crews to cover their mouth and nose with soaked bandages in the long tunnels.

In 1924 the electrification of the line was completed with the activation of the long section from Ronco Scrivia to Turin Porta Nuova.

In 1963 the new Granarolo Tunnel was opened, which allowed the direct connection of the station Genova Piazza Principe from the Giovi second pass, skipping the busy junctions around Sampierdarena, significantly reducing the time taken by long-distance trains.