Born in Milan, Eugenio Siena, a cousin of Giuseppe Campari, joined Alfa Romeo as a young apprentice. Campari helped him get started in motor racing as a mechanic for Scuderia Ferrari. He made his competition debut as a riding mechanic for Enzo Ferrari himself in the early 1920s. Well respected, he also acted at various times as co-driver for Baconin Borzacchini, Mario Tadini, Piero Taruffi, Emilio Villoresi and Tazio Nuvolari, with whom he finished 2nd in the Mille Miglia in 1934 driving an Alfa Romeo 8C 2300 Monza.
He eventually took the wheel, becoming the chief test driver for Scuderia Ferrari in 1930 and also occasionally racing for the team. His finest achievement came in 1932, winning the 24 Hours of Spa-Francorchamps in 1932 sharing an Alfa Romeo 8C 2300MM with Antonio Brivio.
He left Scuderia Ferrari in 1934 and set up his own team under the Scuderia Siena banner racing Maseratis. He finished 8th in the 1934 Monaco Grand Prix in a Maserati 8C and in 1937 took a win driving a Maserati 4CM in the Circuito di Milano voiturette race at Sempione Park.
At the end of 1937 Siena was offered a works drive with Alfa Romeo. His first race for the team, the Grand Prix of Tripoli on 15 May 1938, fataly became his last. One of four works entries along with Giuseppe Farina, Clemente Biondetti and Raymond Sommer, the race held on the Mellaha circuit near Tripoli had a first prize, linked with the Italian Grand Prix of 4 millions Italian lire, worth at that time about 8 million dollars.
The race had a mix of GP and Voiturette cars with a number of the voiturettes getting away early. So at the first corner a number of the GP cars were stuck behind the slower voiturettes.
Siena, who had qualified in 8th, was one of the drivers caught behind the slower cars. He was running in 10th position, just behind the leading pair of voiturettes, the Maserati's of Luigi Villoresi and Franco Cortese. At the start of 8th lap, he passed Cortese at the first corner but, braking hard, he lost the control, hit a sand dune and crashed into a wall of a house. Siena was thrown out and died instantly.
Minutes later another fatality marred the event, when on 11th lap László Hartmann in a Maserati collided with Giuseppe Farina's Alfa Romeo. He broke his spine and died the following day at the Italian Hospital of Tripoli.