McDormand was born Cynthia Ann Smith in Gibson City, Illinois. She was adopted at one and a half years of age by Noreen (Nickelson) and Vernon McDormand and renamed Frances Louise McDormand. Her adoptive mother was a nurse and receptionist while her adoptive father was a pastor; both were originally from Canada. McDormand has said that her biological mother, to whom she proudly referred, along with herself, as "white trash," may have been one of the parishioners at Vernon's church. She has a sister, Dorothy A. "Dot" McDormand, who is an ordained Disciples of Christ minister and chaplain,[4] as well as another sibling, both of whom were adopted by the McDormands, who had no biological children.

McDormand is known for her portrayals of unique, quirky, and headstrong female characters, She is the recipient of numerous accolades, including two Academy Awards, two Primetime Emmy Awards, and a Tony Award. She is one of the few performers to achieve the "Triple Crown of Acting." McDormand was educated at Bethany College and Yale University. She has starred in a number of films by the Coen brothers, including Blood Simple (1984), Raising Arizona (1987), Fargo (1996), The Man Who Wasn't There (2001), Burn After Reading (2008), and Hail, Caesar! (2016). For her portrayal of Marge Gunderson in Fargo, McDormand won the Academy Award for Best Actress. Her other film roles include Mississippi Burning (1988), Almost Famous (2000), and North Country (2005), all of which earned her nominations for the Academy Award for Best Supporting Actress.

In 2011, she won the Tony Award for Best Actress in a Play for playing a troubled single mother in Good People. On television, McDormand played the titular protagonist in the HBO miniseries Olive Kitteridge (2014), which won her the Primetime Emmy Award for Outstanding Lead Actress in a Limited Series or Movie.

In 2020, she starred in and produced the acclaimed independent western drama film Nomadland and recently won a BAFTA, best actress for her portrayal as Fern.