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"Prince Miteb and Mohammed bin Nayef, they are in charge," the adviser said. The world will see a "new strategy for Syria—quieter, more open, not too extreme. There will be more politics to it, and probably much less military." U.S. officials said Prince Mohammed enjoys good relations with Secretary of State John Kerry and CIA Director John Brennan. The latter first met the prince in 1999, shortly before he left Saudi Arabia after serving as the CIA station chief there. The officials also credit the prince with providing intelligence that foiled at least two al Qaeda bomb plots against Western targets.

The changes put the Syria efforts in the hands of princes who are believed to have been among the most cautious among top royals about aggressively supporting the rebels. The U.S. wants to see the moderate rebels it supports fight both the regime and radical fighters such as the al Qaeda-inspired Islamic State of Iraq and al Sham (ISIS). Increasingly, this is happening on the ground in Syria. "You could see a smarter Saudi approach, one more targeted on the Assad regime and one also targeting extremists," said Andrew Tabler, a senior fellow at the Washington Institute think tank. "It seems as if they continue to back the rebels. I think the question is what will that entail."

Prince Mohammed, as a leading counterterror figure globally, is in a position to assuage American fears that if the West supplies weapons, they will wind up in the possession of radicals, said Mustafa Alani, a security analyst with the Gulf Research Center who is close to Saudi security and intelligence circles. "The Americans have to change their policy, and Prince Mohammed is the right person to take this mission.…He's the one who can calm their worries," Mr. Alani said. Saudi officials have told their American counterparts that they intend to ramp up their support for the moderate opposition after the collapse of peace talks in Geneva last month. U.S. officials say they haven't given the Saudis a green light to move forward with plans to give shoulder-fired missiles that can bring down jets to hand-picked rebels. But it is unclear to what extent the U.S. would move to block the Saudis if they insisted on going ahead with the deployment of the weapons over Washington's objections.

Prince Mohammed's appointment reflects shifting U.S. interests in the conflict, with both the Americans and Saudis increasing their focus on countering al Qaeda-linked groups in Syria. U.S. and European officials fear these groups could plot attacks against the West from camps in Syria and that foreign fighters now in Syria will pose a significant threat when they return home to Europe, the Gulf and the U.S. The U.S. has gradually expanded its involvement in Syria at the urging of the Saudis, though not nearly as quickly as the Saudis had hoped. The Saudis persuaded the CIA to pay salaries to some fighters of the Western-backed Free Syrian Army rebel group, and the payments started about a year ago.