The cartoonist will serve as executive producer on the half-hour comedy alongside John Lesher, reports Variety.
The logline reads: "After inheriting a shabby apartment building in a remote California town, a volatile college professor with Utopian delusions drags his family into the unforgiving netherworld of small-town America."
Little Miss Sunshine partners Jonathan Dayton and Valerie Faris have expressed an interest in directing the show.
"We just looked over the script and it's still very early, but we're excited by trying to do something in TV, particularly at a place like HBO, where you can have nine hours instead of two," said Dayton.
Clowes has written various screenplays, including the Oscar-nominated adaptation of his own Ghost World graphic novel.
His book Wilson is being developed into a film by Alexander Payne.