LUCCA, Italy — Secretary of State Rex W. Tillerson said on Tuesday that the reign of President Bashar al-Assad of Syria was “coming to an end” and warned that Russia was at risk of becoming irrelevant in the Middle East by continuing to support him.

Mr. Tillerson, in comments made just before he traveled to Moscow for a high-stakes summit meeting, sought to clear up the United States’ position on Syria while also declaring that President Vladimir V. Putin of Russia needed to choose whether to side with Mr. Assad or the West.

Russia can be a part of the discussions “and play an important role,” Mr. Tillerson said at a Group of 7 meeting in Lucca, Italy, or it “can maintain its alliance with this group, which we believe is not going to serve Russia’s interests longer term.”

In a preview of his coming meetings in Moscow, he then added, “Only Russia can answer that question.”

The United States carried out cruise missile strikes last week after a chemical weapons attack in Syria — where a civil war has raged for six years — that has been widely attributed to Mr. Assad and his military forces.

Russia’s increasingly close alliance with Mr. Assad has allowed it to expanded its military presence in the Middle East and has contributed to what is widely viewed as a renewed relevance in the region. Mr. Tillerson’s suggestion that Russia’s ties with Mr. Assad would diminish the country’s standing contradicts Moscow’s recent experience.

With his comments, Mr. Tillerson tried to untangle the confusing mix of signals from the Trump administration over whether the United States conducted the missile strike for humanitarian or national security reasons, and whether the Trump administration seeks an immediate change in government in Syria.

“We do not want the regime’s uncontrolled stockpile of chemical weapons to fall into the hands of ISIS or other terrorist groups who could and want to attack the United States or our allies,” he said at a brief news conference in Lucca, referring to the Islamic State. “Nor can we accept the normalization of the use of chemical weapons by other actors or countries in Syria or elsewhere.”

Shortly after speaking, Mr. Tillerson got up from a round wooden table in the Palazzo Ducale, where he was attending a summit meeting of foreign ministers from G-7 countries, and headed to the airport.

Mr. Tillerson said that the American priority in Syria and Iraq “remains the defeat of ISIS,” and that Mr. Assad does not have a place in Syria’s future.

“I think it is clear to all of us that the reign of the Assad family is coming to an end,” the secretary of state said. “But the question of how that ends, and the transition itself could be very important, in our view, to the durability, the stability inside of a unified Syria.”

“We are not presupposing how that occurs,” he said, but added that Mr. Assad’s continued use of chemical weapons had ended his legitimacy.

Despite the blunt criticism from Mr. Tillerson, the Italian foreign minister, Angelino Alfano, said there was “no consensus” on whether to toughen sanctions on Russia, as sought by his British counterpart, Boris Johnson.

Mr. Alfano said that any effort to isolate Russia “would be wrong,” adding that the dominant position at the G-7 “was dialogue with Russia, not pushing Russia into a corner.”

The Italian government has long been uneasy about punishing Russia, which faces sanctions imposed for its actions in eastern Ukraine, because many Italian companies have significant business interests there.

“Russia has the power to put pressure on Assad,” Mr. Alfano said.

Mr. Tillerson’s trip to Moscow is the first by a high-level Trump administration official, and the State Department is not expecting any breakthroughs with the Russian government over the myriad issues that increasingly divide the two governments, according to a senior American official.

Rather, the purpose of the trip is to make plain the areas of disagreement, said the official, who spoke on the condition of anonymity in keeping with State Department practice.

Even though Mr. Tillerson received a friendship award from Mr. Putin’s government when he served as chief executive of Exxon Mobil, he has taken a tough line on Russia since joining the administration. He repeated his view that Russia was either incompetent or inattentive in its failure to secure and destroy Mr. Assad’s chemical weapons stockpiles.

“But this distinction doesn’t much matter to the dead,” he said. “We can’t let this happen again.”

Russia has denied that Mr. Assad conducted a chemical attack, saying the poison gas was the result of an assault by rebels. But Mr. Tillerson said he hoped to convince the Russians that their continued support of Mr. Assad has become embarrassing for Russia.

“And now Assad has made the Russians look not so good,” Mr. Tillerson said.

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