In 2013, at just 13-years-old, Stefano Manzi entered the Red Bull Rookies Cup and managed second at the Sachsenring. The following year he was a regular podium finisher, taking seven in total, which saw him finish third in the final standings. He was third again in 2014, this time with nine podiums including a maiden victory at Misano.

The Italian then entered the Moto3 World Championship for 2015, and ended the season as a regular challenger for points. The following year, he took part in just three Moto3 rounds, but managed a best result of fourth at Silverstone. 

2017 saw Manzi step up to Moto2 with his best result coming once again at the British venue, where he managed a seventh-place finish. Over the next four seasons he would become a regular top-10 finisher, with his best result (fourth) coming at the Valencia finale in 2019.

In 2022, he switched to the FIM Supersport World Championship with Triumph. After a solid start, he achieved a double podium result at Most, followed by another third-place finish at Barcelona. His maiden victory came at Portimao while he impressed on his first outing at Mandalika to finish second. 

After finishing sixth in the standings, the championship-winning Ten Kate Yamaha WorldSSP Supported Team signed Manzi for 2023, where he hopes to challenge for the title on board a Yamaha R6 machine.