His death after three decades on the Supreme Court bench, coming 11 months before a new American president takes office, could potentially tip the balance of the highest court in the land from its current 5-4 conservative majority to a liberal one.
The flag outside the Supreme Court was lowered to half- staff in tribute to its longest-serving justice, who died in his sleep while on a hunting trip in Texas according to media reports.
President Barack Obama was informed of Scalia's passing and extended his condolences to his family, the White House said.
The Supreme Court's conservative majority had recently stalled key efforts by Obama's administration on climate change and immigration, and the future of the court is set to become a focus of the 2016 presidential campaign.
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With Scalia's death, all three branches of the US government are now in play come the November general election in which voters will pick a new president as well as new seats in the Senate and the House of Representatives.
The process will be acrimonious at best, with Obama's Democratic administration facing a Republican-held Congress.
The Senate Republican majority leader reacted swiftly by saying the vacancy left by Scalia's death should not be filled before the end of Obama's mandate.
"The American people should have a voice in the selection of their next Supreme Court Justice," Mitch McConnell said in a statement. "Therefore, this vacancy should not be filled until we have a new president."
"It would be unprecedented in recent history for the Supreme Court to go a year with a vacant seat. Failing to fill this vacancy would be a shameful abdication of one of the Senate's most essential Constitutional responsibilities," Reid said.
Scalia was first appointed to the Supreme Court in 1986 by President Ronald Reagan, making him the first Italian- American to serve there.