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NOTE: This spoiler was submitted by Jeremy
The film starts with a short documentary on Rucker Park Legends. Famed basketball players like Dikembe Mutombo and Steve Nash talk about one of the all-time greats, Uncle Drew (Kyrie Irving). He was exceptionally great at the game and would play with a team of his own, but they split up after Drew allegedly slept with one of his teammates' girlfriends.
In the present, we meet Dax Winslow (Lil Rel Howery), a basketball coach. He is visited by his childhood nemesis Mookie (Nick Kroll), who seeks to take Dax's star player, Casper (Aaron Gordon). Dax tries to appeal to Casper and ask him if he needs anything. Knowing Dax works at a shoe store, he requests a new pair of Jordans, which Dax says he will secure for Casper once they arrive.
Dax has a recurring nightmare of his childhood when he lived in an orphanage and was never adopted, but he took an interest in basketball and was really good at it until Mookie blocked his shot and cost him a game, losing everyone's respect. Dax now lives with his girlfriend Jess (Tiffany Haddish) in her apartment and is basically mooching off of her.
At the shoe store, Casper and his buddies come in hoping for Dax to hook them all up with a pair of shoes. Dax doesn't have enough money to cover the expenses, so Jess has to help him out. Dax promises that Casper is going to elevate them since Dax has entered his team into the Rucker Classic basketball tournament.
Dax returns to the gym with new jerseys for the team, only to find out that Mookie has taken over as coach. Dax gets pissed and tries to pull Casper's shoes off of him, and the video of him doing so goes viral. Disgraced and with no team or money, Jess kicks Dax out.
Now homeless, Dax goes around trying to find guys to join his team, to no avail. While watching some guys play at a court, Uncle Drew, who is now elderly, comments on how poorly the guys are playing. They overhear and challenge him to put his money where his mouth is. Drew proves that he's still got it in front of a crowd of impressed viewers. After the game, Dax approaches Drew and asks him to join his team. Drew refuses until Dax manages to convince him. Drew says he will only join Dax if he can get his old team together. Dax reluctantly agrees and joins Drew on a road trip to DC to find the guys.
Dax and Drew stop at a church to find Preacher (Chris Webber), who works as...a preacher. He is baptizing a small baby, but his methods of handling the baby ("Steph Curry-ing" as Dax puts it) frighten Dax to the point that he has to speak up and stop the baptism. He is baptized in the baby's place. Drew then tells Preacher that they are trying to get the team back together, but Preacher's wife Betty Lou (Lisa Leslie) adamantly refuses to let him play again. Dax and Drew almost leave until Preacher tries sneaking with them onto Drew's van. Betty Lou immediately catches wind of this and chases after them in her van, but they lose her.
The guys then go to an arcade where another old teammate, Lights (Reggie Miller), is playing. He appears to be blind, as he misses every shot he takes and can't even see the guys when they approach him. Lights quickly agrees to join them. They then head to a retirement home to find Boots (Nate Robinson), who hasn't walked in years. He is watched by his granddaughter Maya (Erica Ash). Drew tosses Boots a ball, and he proves his reflexes and instincts are still as good as they used to be when he quickly catches the ball. The guys try to find a way to break Boots out of the home, but he manages to roll himself out of the building and join the guys. Maya goes along with them.
The last guy on their team is Big Fella (Shaquille O'Neal), who has not spoken to Drew since the team split up. He now works as the sensei of a karate dojo. The guys approach Big Fella, who sucker-punches Drew. Despite his grudge against Drew, Big Fella agrees to go with the guys, but he refuses to talk to Drew.
On their way back to Harlem, Dax sees he has no money for gas. He spots a girls basketball team and approaches their coach with a bet for $100 to see whose team wins. The girls prove to be much better than the older men, and Dax tells Drew that he needs them to be good because of the bet he made. His team loses, but Drew and the guys pool their money together to pay off Dax's bet and get him gas money.
The team begins to play in the tournaments. Drew's team is off to a good start, but Big Fella doesn't play along properly because of his grudge. After they win the game, he and Drew pay a visit to the grave of Big Fella's wife Jennifer, whom Drew slept with back in the day. He never apologized for it, and that's why Big Fella has always been mad at him. Drew admits that he fell in love with Jennifer too. He apologizes, and Big Fella forgives him.
The team plays another game and wins. They go to a nightclub to celebrate and are challenged by a group of youngsters to a dance-off. The old men prove that they got moves on the dance floor as well. Afterwards, Dax and Maya share a moment, and the guys watch as he appears to nearly kiss her, but he chickens out from insecurity.
During their next game, Big Fella suffers a heart attack. He is out of the game, and the team is found by Betty Lou. She drops her anger at Preacher and then joins the team.
The team then plays in the final game against Mookie and his team. Making things worse is that Jess is now dating Mookie. After a rocky start, Drew and the guys start to play well until he and Casper collide into the net post. They are both taken out of the game, forcing Dax to step into the game for the last minute. Mookie also steps in for Casper, which scares Dax because he is afraid of losing to Mookie again and being humiliated. After some encouragement from the team, Dax manages to psych Mookie out and throw the winning shot. His team cheers him on, Mookie shows him the respect he never gave him, and Dax finds the courage to finally kiss Maya.
The team visits Big Fella in the hospital after their win. He is proud of all of them. They then watch the news report on ESPN on how Dax went from a joke to a hero.
During the credits, Jess tries to call Dax and get him back, but he never responds. Also shown is footage of how the movie's basketball stars underwent the prosthetics and make-up to make them look old.
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Basketball coach Dax Winslow loses his team to his childhood rival Mookie, so he finds the legendary Uncle Drew and recruits him to put his old team back together to play in the Rucker Classic basketball tournament. Dax joins Drew as they go around DC looking for the guys - Preacher, Lights, Boots, and Big Fella.
Drew and Big Fella have been in a grudge since Drew slept with the woman who would become Big Fella's wife. After Drew apologizes, the team starts to play well until Big Fella has a heart attack. Preacher's wife Betty Lou joins the team. Dax also gets close to Boots's granddaughter Maya.
The team plays against Mookie's team in the final game, but after Drew and Mookie's star player are both taken out of the game, Dax is forced to step in and face Mookie once again. Dax manages to score the winning shot. Not only has he redeemed himself in the game, but he has found a real family with his team.
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