Born in Prague, Petr Popelka studied double bass at the Prague Conservatory and the Hochschule für Musik Freiburg. From 2010 to 2019, he served as deputy principal double bassist with the Staatskapelle Dresden, where his interest in conducting developed. In 2019, Popelka became the first conductor fellow of the NDR Elbphilharmonie Orchester, working closely with Alan Gilbert. He subsequently served as chief conductor of the Norwegian Radio Orchestra in Oslo (2020–2023).

The 2025-26 season saw his debuts with the Berlin and Munich Philharmonic, as well as returns to the Gewandhausorchester Leipzig, the Chicago Symphony Orchestra and The Cleveland Orchestra. In 2024, he conducted the Nobel Prize Concert with the Royal Stockholm Philharmonic Orchestra. As an opera conductor, he has led productions at the Zurich Opera House, Deutsche Oper Berlin, Bayerische Staatsoper, and Semperoper Dresden.

Popelka's recordings with the Prague Radio Symphony Orchestra include the complete symphonic works of Smetana, which received the Diapason d'Or de l'Année in January 2026. He is also active as a composer.