Grammer will star as the mayor of Chicago who is diagnosed with a degenerative mental condition that only he and his doctor know about. Described as a modern-day "King Lear," the series will explore political power in the Windy City.
Farhad Safinia ("Apocalypto") wrote the script on spec, with Grammer and his company giving their input.
The "Frasier" star will exec produce with his new Grammnet Prods. partner Brian Sher, as well as Van Sant and Stella Stolper.
The project was the subject of a Hollywood bidding war, and Starz emerged victorious by giving it an 8-episode, straight-to-series order. "Boss" represents Grammer's first foray into drama, as well as his cable debut.
Lionsgate Television is producing "Boss," which was packaged by WME. Coincidentally, WME topper Ari Emanuel's brother Rahm is now running for mayor of Chicago.
Grammer's last TV show was ABC's short-lived series "Hank." He has been producing CBS' "Medium" for years, although the network confirmed on Thursday that it had canceled the supernatural drama.
Safinia is currently adaptating Aldous Huxley's "Brave New World" for director Ridley Scott and star Leonardo DiCaprio, as well as Sony's untitled Allen Counter project that has Will Smith attached to star and produce through his company Overbrook Entertainment.
The writer is represented by Sher's Category 5 management and production company, while WME represents Grammer and Van Sant.