The station is served by high-speed TGV trains to Southern and Eastern France, Switzerland, Germany, Italy and Spain.

It was a boardwalk building designed by architect François-Alexis Cendrier [fr] under the direction of Baron Haussmann, and at the time of its construction it was awaiting arbitration between the French state and the first Compagnie des chemins de fer de Paris à Lyon et à la Méditerranée (PLM) company over its management.

[5] As the station became unsuitable for further expansion, a second Gare de Lyon building was constructed in 1855 by the design of the architect François-Alexis Cendrier.

A portico to the right of the entrance to the arrival hall connected the station itself to the Bâtiment X, the central administration building on the side facing Boulevard Mazas.

[6] By 1900, in time for the 1900 World's Fair, a new thirteen-track Gare de Lyon building was constructed, designed by the Toulon architect Marius Toudoire and decorated with a large fresco by the Marseille artist Jean-Baptiste Olive, depicting some of the cities to which one could take a train from this station.

The station houses the Le Train Bleu restaurant, which has served drinks and meals to travellers and other guests since 1901 in an ornately decorated setting.

International services operate to Italy: Turin and Milan; Switzerland: Geneva, Zürich, Basel and Lausanne; and Spain: Barcelona.