NEW YORK—Secretary of State Hillary Clinton intensified American efforts to woo Syria into backing the U.S.'s Middle East strategy, holding her first direct meeting with her Syrian counterpart in a bid to find common ground on Iran, Lebanon and the Arab-Israeli dispute.

But Damascus's top diplomat, Walid Moallem, in an hourlong interview Monday, voiced opposition to many of the Obama administration's top regional initiatives, and expressed skepticism about the prospects for renewed Syrian-Israeli peace talks.

Mr. Moallem said Damascus would oppose United Nations efforts to issue indictments to support the U.N. investigation into the 2005 murder of former Lebanese Prime Minister Rafik Hariri, a crime some Lebanese officials have blamed on Syria.

The Syrian diplomat ruled out any further cooperation with a U.N. probe into evidence that Damascus had been covertly developing a nuclear reactor along the Euphrates River before Israeli jets bombed the site in 2007.

Mr. Moallem said the U.N.'s nuclear watchdog, the International Atomic Energy Agency, discredited itself last week by failing to approve an Arab-led initiative that seeks to place Israel's nuclear infrastructure under IAEA safeguards.

"It is discredited, the agency," Mr. Moallem, 69 years old, said in the interview in a mid-Manhattan hotel. "It shows how much politics is inside their work. But more, it shows double-standard policies."

Damascus has for years denied any role in Mr. Hariri's death, as well as accusations that it was seeking to develop nuclear weapons in cooperation with North Korea.

Senior U.S. officials have increasingly sought to engage Syrian President Bashar al-Assad in a bid to gain Damascus's support on a range of Mideast issues, as well as to weaken its strategic alliance with Iran. Syria and Iran partner closely in arming and financing the main Arab groups fighting Israel—Hamas in the Palestinian territories and Hezbollah in Lebanon. Syria also has close ties to many of the political factions currently seeking to form a new Iraqi government.

U.S. officials believe a resumption of direct Israeli-Syria talks over the status of the Golan Heights region—a process that broke down in 2000—could diminish Syrian support for Hamas and underpin the separate Israeli-Palestinian peace track.

State Department spokesman, P.J. Crowley, said later Monday Mrs. Clinton and Mr. Moallem discussed a range of regional issues and that Mrs. Clinton "expressed her commitment to securing a comprehensive peace." Mr. Crowley said Syria's foreign minister voiced his own government's interest in peace talks and that Washington and Damascus "would explore ways to move the process further."

Still, Mr. Moallem said he believed a comprehensive Arab-Israeli peace would be doomed without Israel's commitment to first freezing any new construction in disputed territories. He said any direct talks between Syria and Israel could begin only after Prime Minister Benjamin Netanyahu committed to restoring the Jewish state's borders with Syria to the pre-June 4, 1967, lines. "So the land is ours. And it's not up for negotiation," Mr. Moallem said.

The Syrian foreign minister stressed that following such a commitment on the Golan, Damascus would be prepared to discuss joint security and water arrangements, as well as normalization of diplomatic ties, with Israel.

Mr. Netanyahu's government has said it won't enter into talks with Syria that have preconditions. Israel also says Syria has been transferring increasingly sophisticated long-range missiles to Hezbollah, a charge Mr. Moallem denied.

Lebanon remains an issue of tension between Washington and Damascus. The U.S. has strongly voiced its support for the U.N. completing its investigation into Mr. Hariri's murder, as well as trying those indicted for the crime at a U.N. court in The Hague.

Mr. Moallem alleged Monday that the U.N.'s work in Lebanon has been irredeemably "politicized" and that Damascus has received word that members of Hezbollah were soon to be formally charged with the murder. He said that such developments risked plunging Lebanon into a new round of sectarian strife and that the U.N.'s investigation should be replaced by a purely Lebanese investigation to ensure fair treatment.

"We are convinced that a condemnation of the prosecutor of this court against Hezbollah will be a factor of disturbance in Lebanon," Mr. Moallem said.

The U.S. and Syria also could clash diplomatically this fall over the nuclear-proliferation issue, as the Obama administration has indicated it would press for the IAEA to have the powers to launch a "special investigation" of Syria's alleged nuclear infrastructure.

Such a move, if pursued by the IAEA's director general, could result in Syria facing a U.N. Security Council censure, and possibly sanctions, if it doesn't comply with the agency's requests for documents and visiting rights.

Mr. Moallem said Syria, as a signatory to the U.N.'s Nuclear Non-Proliferation Treaty, would continue to allow the IAEA to visit Damascus's research reactor, which is included in his country's formal cooperation agreement with the U.N. body. But he said the IAEA wouldn't be allowed to return to the Euphrates site.

"They know that this case is baseless," Mr. Moallem said. "Of course, to have a nuclear program, a military one, we need to invest billions of billions of dollars. We are not advocating a race for nuclear weapons in the region, on the contrary."

The Syrian diplomat said Mr. Assad has grown disappointed with the pace and scope of President Barack Obama's administration's effort to rebuild ties with Syria over the past 18 months.

The White House's special envoy to Syria, George Mitchell, has visited Damascus and outlined ways that pervasive American sanctions on the Middle East country could be eased to facilitate high-tech trade and the shipment of spare parts for airplanes, according to U.S. officials. But so far, Mr. Moallem said, these steps have had little impact inside Syria.

"Until today—nothing," he said.