Born in Madrid, Herrero purchased his first motorcycle at the age of 12. He obtained his racing licence in 1962, initially competing on a Derbi while performing his own mechanical work. After impressing Luis Bejarano, owner of the Spanish motorcycle marque Lube, Herrero was given a role in the company's competition department. He finished third in the 125cc Spanish National Championship in 1964 and second in 1965, but Lube went out of business shortly thereafter.
Herrero subsequently ran a motorcycle repair shop in Bilbao while racing as a privateer on a Bultaco. His mechanical aptitude attracted the attention of Eduardo Giró, the lead designer at Ossa, who was developing an unconventional race motorcycle with a monocoque chassis. Giró recruited Herrero to help develop the Ossa 250cc racer. The monocoque frame offered exceptional rigidity and light weight, giving the bike superior cornering and braking capability. Together, Herrero and Giró won the 250cc Spanish National Championship in 1967.
Herrero made his World Championship debut in 1968. Despite the Ossa producing approximately 20 horsepower less than the dominant V4 Yamahas of Phil Read and Bill Ivy, the Spanish machine weighed some 20 kilograms less, and its handling was markedly superior on tighter circuits. Herrero finished seventh in the world championship and claimed a third place at the final round at Monza, demonstrating that the Ossa was a genuine competitive proposition.
The 1969 season transformed the competitive landscape when the FIM restricted 125cc and 250cc machinery to two cylinders and six-speed gearboxes, prompting Yamaha and Suzuki to withdraw their factory teams. The change suited Herrero and the Ossa perfectly.
He began the year with a victory at Jarama in front of his home crowd, then added wins at Le Mans and Spa. A crash in the rain at the Ulster Grand Prix broke his left arm, but three weeks later he returned to finish fifth at Imola, a result that drew admiration across the paddock. Going into the final round at the Opatija street circuit in Yugoslavia, Herrero led the world championship by a single point. He led the race before crashing on the seventh lap, surrendering the title. He finished third in the championship overall and won the Spanish national title for the third consecutive year.
Herrero started 1970 with second place in France and a victory in Yugoslavia before the series moved to the Isle of Man. During the sixth and final lap of the 250cc Lightweight TT, he crashed at Westwood Corner after losing control on melted tar. He had already recovered from an earlier incident at Braddan Bridge during the same race. Despite regaining third place, the second crash proved fatal. Herrero died two days later on 10 June 1970, aged 27.
The loss of Santiago Herrero devastated the Ossa factory so profoundly that the company abandoned Grand Prix road racing altogether. He remains one of the most admired Spanish motorcycle racers of the pre-modern era, remembered both for his remarkable mechanical intelligence and for the spirit with which he pushed an underpowered machine to within a single point of the 250cc world championship.