Colombo began his career as an apprentice to Vittorio Jano, the celebrated designer who had defined Alfa Romeo's dominance in grand prix racing throughout the 1920s and early 1930s. In 1937 Colombo designed the engine for the Alfa Romeo 158, the car known as the Alfetta, which would go on to dominate the first two seasons of the Formula One World Championship in 1950 and 1951. The quality of this work caught the attention of Enzo Ferrari, who was in the process of establishing his own manufacturer marque and needed a capable engine for his racing and road car programme.
Ferrari commissioned Colombo to design a compact V12, and the result made its public debut on 11 May 1947 in a 1.5 litre form, first fitted to the Tipo 125. The same basic architecture was subsequently used in the Tipo 159 and 166 sports cars. The engine's fundamental design proved extraordinarily adaptable: over the following decades it was enlarged to displacements as large as 4.8 litres and used in road cars and endurance racing cars — most notably the Ferrari 250 series, the 3.0 litre racing, sports, and GT cars that defined Ferrari's identity in the late 1950s and 1960s.
Despite the longevity of the engine's road car applications, the Colombo V12's performance in Formula One competition proved less convincing. The naturally aspirated unit showed early promise in the Ferrari 166, but when the engine was supercharged for grand prix use it failed to match the performance of its rivals. Ferrari responded by engaging Aurelio Lampredi to develop a large, naturally aspirated V12 as an alternative, and Lampredi's design eventually displaced Colombo's within the Formula One programme. Colombo departed Ferrari in 1950.
Returning to Alfa Romeo, Colombo oversaw the company's racing efforts during the period of its greatest Formula One success. The Alfa Romeo 158/159 Alfetta, the car whose engine he had originally designed in 1937, won the inaugural Formula One World Championship with Nino Farina in 1950 and repeated the title with Juan-Manuel Fangio in 1951.
In late 1952 Colombo moved to Maserati, where he created the 250F Grand Prix car, a design that would become one of the defining racing machines of the mid-1950s and the car in which Fangio won his 1957 world championship title under a different design era. Two years after joining Maserati, Colombo moved again — this time to the newly revived Bugatti company, where he worked on the Bugatti 251. He subsequently joined MV Agusta, where he remained from 1957 to 1970, contributing to that company's motorcycle and automotive engineering efforts.
Gioacchino Colombo died in Milan on 24 April 1988. His contribution to automotive engineering is difficult to overstate: the Alfa Romeo 158 engine he designed in 1937 powered two Formula One world champions, while the Ferrari-Colombo V12 he created a decade later became the genetic basis for road and competition cars that endured for more than four decades. His career traced the principal lineage of Italian performance engineering — from Jano's Alfa Romeo to Ferrari's founding years to Maserati's grand prix programme — and he documented his own perspective on this history in his memoir Origins of the Ferrari Legend, published in 1985.