Uncle Buck is a charismatic hustler who has gotten by on his charm for years. But when his brother Will and sister-in-law Alexis move to town and need help with their kids, he steps up to become their "manny". Their lives will never be the same.

Alexis and Will try to help Maizy overcome her shyness in order to sell Sunny Scout cookies. Mom does her best to teach Maizy the valuable lesson of following the rules by selling cookies the right way, while Dad just wants to get rid of them by any means possible. When both plans fail, Buck jumps in to help Maizy break out of her shell and hustle her way to the top - as only he can.

Alexis insists on riding along with Buck on his first day as nanny. But as Buck deals with a cranky school principal, searches for gluten-free cupcakes and stages a small break-in to obtain special food for the family's allergic dog, he drives Alexis to the brink. Back home Will tries to prove that he's capable of taking care of Miles, who is home sick from school.

Sibling rivalry gets the best of Will when Buck really hits it off with his architect office buddies. Rivalry of another kind spurs Alexis to drag her reluctant kids into a lip-sync battle hosted by the snooty president of her college sorority alumna.

Alexis is convinced that Buck is to blame for Miles' new, impulsive attitude after she catches him attempting a risky stunt for his Youtube channel. With Miles' punishment looming, Buck decides to throw a "going to jail" party while Mom and Dad are out, but unfortunately a creepy neighbor calls the cops and ruins their celebration. Buck, Miles, Tia and Maizy seek revenge and end up in a prank war.

Buck and his buddy Cy have a tradition of watching the Bulls games on TV together with Buck's lucky basketball beside them (or the Bulls lose). But Buck's multi-tasking skills are pushed to the limit as Tia, Miles and Maizy all have separate crises on the night of a big game, and Will and Alexis are out celebrating their anniversary.

Will and Alexis return from a day out to find the house in complete chaos, with a broken window, a wading pool full of ice, a disabled wood chipper and a small fire burning in the yard. But when they try to get to the bottom of things, Buck and the kids all have different versions about what really happened.

Buck takes the whole family back to his and Will's old South Side neighborhood after he realizes the kids have no idea what life growing up there was really like.