In the final game coming out of a timeout with mere seconds left on the clock, Uncle Drew (Kyrie Irving) reminds Preacher (Chris Webber) that they have no more timeouts. This is in reference to an incident during the NCAA Men's Division I Basketball Tournament on April 5, 1993. During that game, the real life Webber called a timeout with 11 seconds remaining in the game. Unfortunately, his team, the Michigan Wolverines, who were down 73-71 against North Carolina, didn't have any timeouts left. The call earned Webber a technical foul, and ended up costing the Wolverines the chance to win. Although Webber went on to have an illustrious career in the NBA, he continues to receive ridicule for that error.

Lisa Leslie, who plays Betty Lou, is a two-time WNBA champion, a five-time Olympic gold medalist, and the first player to dunk in a WNBA game.

In the outtakes during the credits, Kentucky Wildcats coach John Calipari asks Uncle Drew if he wants to play for his team. Uncle Drew tells him "No, I'm more of a Blue Devils guy." Kyrie Irving briefly played for the Duke Blue Devils before turning pro.

Shaquille O'Neal has always been a huge break-dancing fan, and a fan of dancing in general. When he was young, his father taught him that basketball was a game of rhythm, and that if Shaq could become a dancer, his dancing skills would translate to the basketball court.

The character played by Lil Rel Howery expresses fear of being in the woods and kidnapped because he's seen the movie Get Out. Howery actually appeared in Get Out as a TSA agent.