The 125 F1 was powered by Gioacchino Colombo's 1.5 L (1497 cc/91 in³) 60° V12. It had a single overhead camshaft on each bank of cylinders with a 60° angle between the two banks. The engine had two valves per cylinder fed through one Weber 40DOC3 or 50WCF carburettor. With just a 6.5:1 compression ratio, the supercharged engine still produced 230 hp (172 kW) at 7000 rpm. However, the Roots-type single-stage supercharger was incapable of producing the high-end power required to compete with the strong eight-cylinder Alfa Romeo 158 and four-cylinder Maserati 4CLT. Strong driving and a nimble chassis, however, allowed the company to place third in its first outing, at the Valentino Grand Prix on September 5, 1948 and the company persevered in racing.
For 1949, the engine was further modified with dual overhead camshafts (though still two valves per cylinder) and a two-stage supercharger. This combination gave the car better top-end performance and the resulting 280 hp (209 kW) gave it five Grand Prix wins. Development continued the following year, but the problematic superchargers were dropped in favor of larger displacement and Lampredi's 275 engine superseded the original Colombo engine.