The rapper hit the stage at the E11EVEN nightclub in Miami, as part of Formula 1 race week celebrations.
The 31-year-old reportedly arrived at 3am, took the microphone and performed in front of the sold out crowd.
He also took a bottle of tequila onto the stage and encouraged fans to take shots.
Before the performance, he had only made appearances at private parties, including before the Oscars and a Coachella afterparty.
It follows the Astroworld event in Houston last November, where fans were crushed in the crowd.
It left 25 people hospitalised and 300 treated at the scene.
Scott faces several lawsuits in relation to the event.