But Prince Nayef's death opens the possibility that a member of the so-called third generation of the royal clan - younger and mostly Western-educated - will now move into one of the traditional ruler-in-waiting roles.
"Saudi Arabia will have to decide if this is the time to set the next generation on the path to rule," said Simon Henderson, a Saudi affairs expert at the Washington Institute for Near East Policy.
First, however, the Saudi leadership must fall behind the replacement for Nayef, the hard-line interior minister who headed Saudi Arabia's fierce crackdown that crushed al-Qaeda's branch in the country after the 9/11 attacks. Nayef, who Al-Arabiya reported died in Geneva, Switzerland, was named crown prince in November after his brother Prince Sultan died.
The Allegiance Council, an assembly of sons and grandsons of the first Saudi monarch, King Abdul-Aziz, will choose the next crown prince.
The likely choice is the 76-year-old Salman, who served for more than four decades in the influential post of governor of Riyadh, the capital, as it grew from a desert crossroads to the center of political power for the Western-allied Gulf states.
Nayef, 78, was seen as closely in tune with Saudi's ultraconservative Wahhabi religious establishment, which gives legitimacy to the royal family and strongly opposes pressures for change such as allowing women to drive or participate on the Saudi Olympic team. Salman also has little inclination to challenge the authority of the clerics or push hard for reforms, experts say.
President Obama said Nayef "dedicated himself to the security of Saudi Arabia as well as security throughout the region."
"Under his leadership, the United States and Saudi Arabia developed a strong and effective partnership in the fight against terrorism, one that has saved countless American and Saudi lives," the White House statement added.
Nayef had been out of the country since late May, when he went on a trip that was described as a "personal vacation" that would include medical tests.
The royal family, which closely guards information about the health of its members, confirmed the death but gave no details. It said the funeral would be held Sunday after prayers in Mecca.