Drake is currently on tour with Migos with three dates set in Houston.
During Sunday's show, Drake and Scott, who hails from Missouri City, performed their new song "Sicko Mode" off of Scott's latest album Astroworld.
Scott, who wore a James Harden jersey, might have been a surprise to fans, but Drake has long made his love for Houston known.
He's made references to the Bayou City in his music and has held a Houston Appreciation Weekend.
Drake has also said that his career started in Houston, with a show at Warehouse Live on May 8, 2009.
Drake used his Saturday show in Houston to honor a Missouri City teen who was killed weeks ago, allegedly by her boyfriend.
"So look, tonight, I just want to start the show a little different," he said. "It's a young girl by the name of Sabrina Herrera, and she was supposed to be at the show tonight. She had saved her money, she had gotten tickets, she had bought an outfit."
Drake said he was also supposed to meet the teen.
Drake will wrap up his Houston stop with a third show on Tuesday night.
Tickets are still available on the Toyota Center website.