The station was built as an addition to the airport to serve TGV trains on the LGV Rhône-Alpes, part of the main line running from Paris Gare de Lyon to Marseille Saint-Charles.

A rail link to La Part-Dieu (main railway station and business district) in central Lyon is provided by the Rhônexpress tram-train line with a 30-minute journey.

Saint-Exupéry station was designed by Santiago Calatrava, cost 750 million Francs and opened on 3 July 1994, at the same time as the high-speed line to Saint-Marcel-lès-Valence.

Lack of interconnection with Lyon's urban transport network is frequently cited for the station's low usage.

The arrival of the Rhônexpress express tram (opened August 2010) is unlikely to change this as Lyon residents will still find it easier (and cheaper) to use the stations within the city.