Tilson was supposed to play for the Batavia Muckdogs in 2012, using the time before the season began to develop his power behind the plate while at extended spring training.

[12] Tilson spent most of 2013 with Single-A Peoria, playing in 100 games before receiving a late season promotion to High-A Palm Beach.

Tilson returned to Palm Beach in 2014, where he made the mid-season Florida State League All-Start team after hitting .298 with 17 RBI in the first half.

[15][16] Tilson was also slated to appear in the Arizona Fall League after the season, but missed out with a stress fracture in his foot.

After the season, Tilson got a chance to play in the Arizona Fall League with Surprise, while also being added to the Cardinals 40-man roster, thereby protecting him from the Rule V Draft.

[19] Tilson began 2016 with Triple-A Memphis, where in 100 games, he hit .282/.345/.407 with 4 HR, 34 RBI, 53 runs, and 15 stolen bases to just 3 times being caught.

On July 31, 2016, the Cardinals traded Tilson to the Chicago White Sox, the team he grew up rooting for, for relief pitcher Zach Duke.

He made his debut against the Detroit Tigers on August 2, and got his first major league hit, a single, in his first at bat, against Aníbal Sánchez.

[23] Unfortunately, Tilson strained his left hamstring during the game attempting to make a diving catch, and was placed on the disabled list, curiously becoming the fourth White Sox member in 2016 to become injured on or before their debut.

[25] Following the offseason trade of Adam Eaton, Tilson was among the favorites to land the center field job out of spring training in 2017, receiving the endorsement of general manager Rick Hahn.

[30] On May 22, Tilson hit a grand slam for his first major league home run off of Astros reliever Josh James.