Writer-director Jordan Peele picked up the trophy for best original screenplay for "Get Out," a dark satire of the African-American experience and liberal white guilt.
"This was a passion project. It was something I put my love into, I put my soul into, so getting this from you means so much," Peele said as he picked up his trophy.
"I started writing it in 2008 and there were a lot of ups and downs."
The film, starring Daniel Kaluuya, has already landed Peele best first time feature at the Directors Guild of America Awards and is nominated for four statuettes at the Oscars, to be held on March 4.
"Get Out" beat out "The Big Sick," "I, Tonya," "Lady Bird" and "The Shape of Water."
The evening was hosted for the third year in a row by Emmy and Grammy-winning actor, writer and comedian Patton Oswalt, who began by light-heartedly chastising the WGA for bringing him back.
Best documentary screenplay went to Brett Morgen for "Jane," a study of the life and work of celebrated primatologist Jane Goodall, whose groundbreaking chimpanzee research revolutionized people's understanding of the natural world.
In the television category, Hulu's "The Handmaid's Tale" won both best drama and best new series, while HBO's "Veep" took best comedy series.
The WGAs is one of Hollywood's last major prizegiving ceremonies ahead of the Academy Awards.