Justice Ruth Bader Ginsburg, a stalwart liberal on the US Supreme Court since 1993, has died at the age of 87, the court said.
It gives President Donald Trump a chance to expand the court's conservative majority with a third appointment at a time of deep divisions in America with a presidential election looming.
Ms Ginsburg, a champion of women's rights who became an icon for American liberals, died at her home in Washington DC of complications from metastatic pancreatic cancer, the court said in a statement.
She was surrounded by her family.
Her departure could dramatically alter the ideological balance of the court, which currently has a 5-4 conservative majority, by moving it further to the right.
"Our Nation has lost a jurist of historic stature," Chief Justice John Roberts said in a statement.
"We at the Supreme Court have lost a cherished colleague. Today we mourn, but with confidence that future generations will remember Ruth Bader Ginsburg as we knew her - a tireless and resolute champion of justice."
Mr Trump, seeking re-election on 3 November, already has appointed two conservatives to lifetime posts on the court,
Neil Gorsuch in 2017 and Brett Kavanaugh in 2018. Supreme Court appointments require Senate confirmation, and Mr Trump's fellow Republicans control the chamber.
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Supreme Court justices, who receive lifetime appointments, play an enormous role in shaping US policies on hot-button issues like abortion, LGBT rights, gun rights, religious liberty, the death penalty and presidential powers.
For example,the court in 1973 legalised abortion nationwide - a decision that some conservatives are eager to overturn - and in 2015 allowed same-sex marriage across the United States.
US President @realDonaldTrump on the passing of US Supreme Court Justice #RuthBaderGinsburg: "She just died? I didn't know that. She led an amazing life, what else can you say? Whether you agree or not ... she led an amazing life." #RBG @rtenews pic.twitter.com/y0DxBrRBG9— Brian O'Donovan (@BrianOD_News) September 19, 2020
Ms Ginsburg, who rose from a working class upbringing in New York City's borough of Brooklyn and prevailed over systematic sexism in the legal ranks to become one of America's best-known jurists, was appointed to the Supreme Court by Democratic President Bill Clinton in 1993.
She provided key votes in landmark rulings securing equal rights for women, expanding gay rights and safeguarding abortion rights.
Ms Ginsburg had experienced a series of health issues including bouts with pancreatic cancer in 2019 and lung cancer in 2018, a previous bout with pancreatic cancer in 2009 and colon cancer in 1999. She disclosed on 17 July 2020 that she had a recurrence of cancer.
Ms Ginsburg was the oldest member of the court and the second-longest serving among its current justices behind Clarence Thomas. She was the second woman ever named to the court, after Justice Sandra Day O'Connor who was appointed 12 years earlier.