Picket lines formed outside film studios in Los Angeles and New York on Tuesday as thousands of writers downed tools.
For the first time in 15 years, some 11,000 union members walked off the job in a protest over pay and conditions in the streaming era.
Late-night shows fronted by the likes of Jimmy Kimmel, Seth Myers, and Stephen Colbert are expected to be the first casualties in the strike.
If it continues, it could also hit television series and films scheduled for release later this year.
The industrial action comes after talks between the Writers Guild of America and the studios' Alliance of Motion Picture and Television Producers collapsed.
The last time Hollywood writers laid down their pens, the strike lasted 100 days and cost the entertainment economy around $US 2 billion.