The 159 S was designed to be the successor to Ferrari's first vehicle, the 125. Unlike its predecessor, which won six of 14 races earlier in 1947, the 159 had a short racing life and was quickly converted into the 166 SC for the following racing season.

Like the 125, the 159 used a steel tube-frame chassis with longitudinal and cross members and had a double wishbone suspension with transverse leaf springs in front with a live axle in the rear. However, Gioacchino Colombo's V12 engine was enlarged from 1.5 L (1497 cc/91 in³) in the 125 to 1.9 L (1903 cc/116 in³) for the 159. This engine produced 125 hp (93 kW) at 7,000 rpm, retaining the three double-choke Weber 30DCF carburettors of its predecessor. Both cars sported five-speed manual transmissions and retained the Fiat tradition of mounting the engine in-block with the gearbox.


One Ferrari 159 was built, with chassis number 002C. The oldest Ferrari car still in existence with an undisputed pedigree is a 166 Spyder Corsa number 002C, which was originally a 159 and is currently owned and driven by James Glickenhaus.


The 159 S debuted on August 15, 1947 at the Circuito di Pescara with the company's driver, Franco Cortese. Although it led overall for a time, the class-winning 159 S eventually fell behind the Stanguellini of Vincenzo Auricchio. Like the 125, the 159 S was unable to beat Maserati's 6CS 1500 for much of the rest of the 1947 season. However, at the Turin Grand Prix on October 12, the car was able to shine, with French driver Raymond Sommer claiming overall victory in the single 159 S entered.