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

His remarks, five days after the United States carried out missile strikes in retaliation for a chemical attack for which Washington and its allies blamed Mr. Assad, illustrated the extent to which the Trump administration has, in just one week, substantially rethought its approach to Syria’s future.

Before the April 4 chemical attack, the administration appeared resigned to letting Mr. Assad’s government, backed by Russia and Iran, continue gaining the upper hand in a six-year-long civil war that has claimed at least 400,000 lives. Even after the attack, Sean Spicer, the White House press secretary, said the administration would look “rather silly not acknowledging the political realities” of Mr. Assad’s grip on power.

But then, late last week, Mr. Trump declared that efforts to change Mr. Assad’s behavior had “failed very dramatically.” Mr. Tillerson said that Mr. Assad could no longer remain in office, and that “steps are underway” for an international effort to remove him. On Tuesday, Mr. Tillerson seemed close to embracing the very policy the Obama administration had decided on: that Mr. Assad would eventually have to cede power, though the timeline remains unclear.

Mr. Trump himself has yet to clarify a welter of mixed signals emanating from Washington.

Mr. Tillerson’s remarks did little to end uncertainty about the Trump administration’s policies, which have cycled through acceptance of Mr. Assad’s long-term hold on power, the need for his immediate removal and something in between.

The remarks at a Group of 7 foreign ministers’ meeting here in the Tuscany region of Italy came just before Mr. Tillerson flew to Moscow to meet with Russia’s president, Vladimir V. Putin.

Mr. Putin, at an appearance with President Sergio Mattarella of Italy, said on Tuesday that the chemical attack was “worth investigating thoroughly,” and he said Russia would formally ask the Organization for the Prohibition of Chemical Weapons for an inquiry.

But Mr. Putin showed no signs of backing away from Mr. Assad. He likened the accusations against the Assad government — made by Britain, France and other allies, along with the Trump administration — to the flawed intelligence that President George W. Bush’s administration cited in 2003 to justify the invasion of Iraq.

Mr. Putin insisted that the chemical attack had stemmed from anti-Assad rebel units.

“We have information from various sources that similar provocations — and I have no other word for that — are being prepared in other regions of Syria, including southern suburbs of Damascus, where they intend to plant certain substances again and accuse official Syrian authorities of using them,” he said, without providing evidence for his claims.

Russia’s increasingly close alliance with Mr. Assad has allowed it to expand 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 of 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 on Tuesday, Mr. Tillerson got up from a round wooden table in the Palazzo Ducale, where he was attending the foreign ministers’ meeting, and headed to the airport, bound for Moscow.

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 he 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 Group of 7 industrialized nations “was dialogue with Russia, not pushing Russia into a corner.”

The Italian government has long been uneasy about punishing Russia, which faces sanctions 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. On Tuesday, 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.”

Mr. Tillerson said he hoped to convince the Russians that their continued support of Mr. Assad has become embarrassing for them.

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

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