Uncle stars stand-up comedian and singer/songwriter Nick Helm as Andy, a dissolute out-of work musician who forges an unlikely alliance with his 12-year-old nephew Errol after being morally blackmailed into looking after him by his chaotic sister Sam – all on the day Andy was planning to kill himself.
For Andy, the seemingly simple task of caring for his nephew spirals into a bizarre misadventure for the pair, involving a faked injury, a car crash, a visit to a gay club, a lot of lying, and some hard lessons in life.
After a series of personal humiliations, Andy’s forced to babysit a sick Errol. But upon learning his nephew is faking illness to get out of a child’s birthday party, Andy’s determined to teach Errol how to be a party monster. Little does Andy know he’ll have to face some monsters of his own at the birthday party from hell.
Andy tries to get back with Gwen by entering a battle of the bands. Only problem, he doesn’t have a band. Errol’s acting weird and it has something to do with a girl. When the guys learn of their mutual woes, they join forces to help each other out. But when Andy tries to turn Errol into a ladies' man, things are bound to get complicated...
Errol's paternal grandmother Joan is hosting a family lunch and Sam ropes Andy into coming along for moral support. Unfortunately it's just as Errol's 'cool uncle' Rex arrives home on holiday and Andy embarks on a competition to win Errol's sole affections. Sam and Ben hit a snag in their custody battle, someone's got a crush on Errol, and Andy doesn't know how to deal with Joan after she reminds him of 'that night'. The scene is set for a delightfully tense day at grandmother's house.
While Sam is attempting to attract a cool new sponsor and Errol is away on a school trip, Andy is trying to break up with Shelly, make up with Gwen and woo Errol's teacher Melodie. But can Andy really juggle three women? With Errol on the phone trying to be his conscience, Andy takes things to farcical extremes to try to have his cake and eat it too.
While Sam is away on a tree-hugging retreat, Andy and Errol are offered the opportunity of a lifetime - to sign with Rage Records and infamous music producer Mo Kahn. Little does Andy know that Mo is only interested in the kid and Errol hasn't worked out how to break the bad news. When a series of seemingly innocuous events puts Errol in mortal danger and the whole custody case in dire jeopardy, can irresponsible screw-up Andy finally make it right?