After Homer dumps a silo of pig waste in to Springfield's lake it becomes dangerously toxic causing the government to not just quarantine the town but place a giant dome over it. But Homer, Marge, Bart, Lisa and of course Maggie go fugitive and escape via a sink hole in their backyard, heading to Alaska where they plan to build a new life. But when they discover that the government has a more sinister plan involving Springfield they return home to save the day and for Homer a change to regain the respect of Bart who had become disappointed in his father.
I think you would have had to be from one of those undiscovered tribes in the Amazon to have never heard of the Simpsons or at least be able to recognize these distinct yellow characters. But here is the curious thing as whilst I knew the characters including those in supporting roles I don't remember having ever watched an entire episode of The Simpsons but watched a bit here and there whilst channel hopping. I mention that because even as someone who only has a casual interest in the long running animation "The Simpsons Movie" is fun.
Now part of this is because the writers have gone down the parody movie route with a style which throws a joke at us every few seconds. So we go from Homer using Maggie to bung up a sink hole in the garden to Bart naked skateboarding through Springfield. It works because all of the jokes are kept in the realms of the Springfield universe with nothing which seems out of context; would Bart pull a naked skateboarding stunt, yes, would Homer walk a pet pig across the ceiling, yes even though it is simply daft. It's not just daft comedy as there is some smart humour in the mix as well whilst all the humour plays it relatively safe with the occasional dig at the government and religious types. Yet none of it demands that you need to know who the Simpsons are.
The other reason why this works is because behind the barrage of humour there is also a story and not just about Homer contaminating Springfield Lake with his silo of pig waste. We see how Bart becomes disappointment in Homer and looks to neighbour Ned Flanders as a better father figure. Of course that means that at some point Homer will have the road to Damascus moment and realise he's been a bad father but it does give all this humour a purpose without being too heavy.
What this all boils down to is that "The Simpsons Movie" works and with its constant stream of humour works as well for those with barely any knowledge of the Simpsons as I hope it does for long-time fans.