YouTube Premium has commissioned a dark comedy co-produced by George Clooney and Kirsten Dunst, who will also star in the series, according to a source familiar with the deal.
YouTube's alliance with two powerhouse names in Hollywood comes as competition intensifies in an online streaming video market with players such as Netflix, Amazon, Hulu, and Apple.
Google-owned YouTube's subscription service Premium offers ad-free viewing of shared videos along with original content for $12 a month.
Original content has become a battlefront in online video, with Netflix and Amazon Prime spending billions of dollars on shows.
The YouTube series titled On Becoming a God in Central Florida will centre on the US cult of unbridled entrepreneurship and a woman's intense pursuit of the American Dream.
The series will be set in the 1990s, and is scheduled for release next year.
YouTube Premium, formerly named YouTube Red, had a hit with its first big original series, Cobra Kai, inspired by the Karate Kid martial arts underdog film from 1984.
The first episode of Cobra Kai has logged more than 40 million views since it was made available at YouTube on May 2 and a second season has been ordered.
Launched in late 2015, YouTube Premium includes an online streaming music service and is seen as part of a broader effort by Google-parent Alphabet to expand how it makes money beyond advertising revenue.