Beginning on Tuesday, the high court will also examine President George Bush's policies in the "war on terrorism".
At issue is whether American courts have jurisdiction. Judges will not consider the conditions of confinement or the extent of the prisoners' legal rights.
Three cases are to be heard over the next two weeks.
They could result in the most important rulings in more than 50 years on the role of the American judiciary in reviewing government policies during wartime.
Justice in war?
The high court is set to weigh civil liberties concerns against national security arguments as the government makes a broad assertion of presidential power.
Steven Shapiro, the American Civil Liberties Union's legal director, said: "These cases raise fundamental questions about the role of the courts in preserving civil liberties."
The justices scheduled 60 minutes of arguments on whether American courts can hear challenges to the legality of the detention of foreign nationals captured abroad.
About 595 foreign nationals, who have been designated "enemy combatants," remain at the base as suspected al Qaida members or Taliban fighters.
"These cases raise fundamental questions about the role of the courts in preserving civil liberties"
American Civil Liberties Union
Most were seized during the US-led campaign against the Taliban government in Afghanistan. The first detainees arrived at Guantanamo in January of 2002.
Only two of the detainees have been charged and face military commissions while four have been given lawyers.
The rest are being held without charges, without access to lawyers and without access to courts or a proceeding of any kind.
John Gibbons, a retired US appeals court judge who was appointed to the bench by Republican President Richard Nixon in 1970, will argue on behalf of the detainees.
In written briefs, lawyers for the detainees said the US constitution does not allow the creation of a prison beyond the reach of the judiciary.
Especially a prision reserved for foreign nationals who may be held "on mere executive fiat".
The administration's position will be argued by Solicitor General Theodore Olson, the government's chief advocate before the Supreme Court.
His wife, Barbara Olson, was among the passengers killed on the hijacked plane that crashed into the Pentagon on 11 September 2001.