This year, the 60-year-old actor had also won a Golden Globe, a BAFTA and Screen Actors Guild Awards for her role in Martin McDonagh's film.
Jennifer Lawrence and Jodie Foster presented the Best Actress trophy to McDormand, in a break from tradition where the previous year's Best Actor winner presents the award.
In her acceptance speech, McDormand thanked her family and asked all the other female nominees to stand up. She also urged producers to back small and independent films
"I have two words to leave with you tonight, 'inclusion' and 'writer'," an emotional McDormand said.
McDormand emerged victorious against Saoirse Ronan ("Lady Bird") Meryl Streep ("The Post"), Sally Hawkins ("The Shape of Water") and Margot Robbie ("I, Tonya").
In the black comedy drama, McDormand plays Mildred, the disillusioned and angry mother of a young woman whose murder has gone unsolved in her small-town American community.
McDonagh wrote the character of Mildred with McDormand in mind. However,the actor was initially not sure about her casting in the role as she is older than the character. Her filmmaker husband Joel Coen convinced her to say yes to the part.
Born on June 23, 1957 in Chicago, Illinois, McDormand earned her BA in Theater from Bethany College in 1979 and her MFA from Yale in 1982.
Since then the couple have collaborated on many films including "Fargo", "Burn After Reading" and most recently "Hail, Ceaser!".
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