The actress picked up the honour in Best Actress in a Motion Picture - Musical or Comedy category for her film "The Farewell". In the film, she is seen as Billi, a Chinese-American woman who travels back to China with her family to say goodbye to her terminally ill grandmother (essayed by Shuzhen Zhao).
A first-time Globes nominee, Awkwafina won over Ana de Armas ("Knives Out"), Cate Blanchett ("Where'd You Go, Bernadette"), Beanie Feldstein ("Booksmart") and Emma Thompson ("Late Night").
"This is great, thank you, if I fall upon hard times I can sell this, so that's good," the actress joked as she got on the stage to accept the honour on Sunday night.
She then thanked her family and the director Lulu Wang.
"You gave me this chance, the chance of a lifetime, and you've taught me so much," she said, adding: "Just filming this story, being with you, is incredible."
According to variety.com, it is the first time a performer of Asian descent has won a lead actress Golden Globe Award for a film. Last year, Sandra Oh became the first Asian woman since 1980 to win best actress in a TV drama for "Killing Eve".
Awkwafina dedicated her award to her father, her grandmother and her late mother.
This was Awkwafina's first Golden Globe nomination. "The Farewell" also received a nomination for Best Motion Picture - Foreign Language.
Last year, the actor-rapper celebrated getting nods through an Instagram post.
She wrote: "This week has been so surreal. Incredibly honored to wake up to the news this morning... Thank you so much HFPA for this nomination and for recognizing @thefarewell. Can't believe I am nominated alongside such insanely talented women."
( With inputs from IANS )