The announcement came as Syrian activists said rockets fired by government forces were seen in the skies above Homs, where a doctor said at least 30 people were killed Monday.
"We have concluded that we need to suspend operations at our embassy in Damascus in light of the fact that we have security concerns about the safety of our personnel," State Department spokeswoman Victoria Nuland said in Washington during the daily briefing.
After discussions over several weeks with Syrian failed, "Ambassador [Robert] Ford and the remaining personnel departed the country Damascus time this morning, and the flag's been taken down," she said.
She said the Polish Embassy would be America's protecting power in Damascus, so any remaining U.S. citizens in Syria who haven't heeded the department's travel warnings can receive consular services though the embassy of Poland, she said.
Before leaving, Ford visited with Syrian Foreign Minister Walid Moallem to formalize the U.S. decision to suspend and to "make clear that we expect the remaining Vienna Convention obligations that they have to our property … will be respected and to formally make clear that the government of Poland will be our protecting power."
She said the diplomatic staff looked forward to reopening the embassy "when there are better days" in Damascus.
"We have suspended our diplomatic presence in Damascus," Nuland said. "We have not broken diplomatic relations, and there's a difference there."
In Homs, people reported killed by a doctor at a field hospital raised the two-day death toll to at least 59 in the city, activists said.
"It is horrible. Especially today, it is horrible," activist Abu Omar told CNN. "Usually they are using mortars. They are now using rockets in the sky. We can see them in the sky."
Syrian state-run TV blamed "armed terrorist groups in Baba Amr," saying they were using mortars to attack several areas in Homs, CNN reported.
The Syrian government stepped up its crackdown on pro-democracy activists after the U.N. Security Council failed to pass a resolution condemning the regime of President Bashar Assad Saturday, activists said.
"The U.N. gave them the green light to inflict more violence," an activist identified as "Danny" told CNN. "If it wasn't for the U.N., they wouldn't have [done] this. It gave them the OK to kill more. If the U.N. had done something about this, this regime would be a little bit scared."
China and Russia vetoed a U.N. Security Council draft resolution sought by the Arab League that, among other things, would have called on Assad to stop the killing and work toward finding a Syrian-led solution to the crisis.
The Local Coordination Committees of Syria said at least 29 of 43 deaths Sunday were in Homs, CNN reported.
Opposition groups said more than 300 civilians had died in the flashpoint city since Thursday.
United Nations officials said an estimated 6,000 people have been killed since protests began nearly a year ago. The LCC had a much higher number, saying at least 7,339 people have been killed. The Syrian government has blamed the violence on armed thugs and terrorist groups.
Foreign media outlets cannot independently confirm the veracity of opposition or government reports from Syria because the government has restricted journalists' access to the country.
Bashar Jaafari, Syria's ambassador to the United Nations, said the crisis was manufactured by a media campaign designed to cast a bad light on the Syrian government, CNN said.
The vetoes by Russia and China drew criticism from several of the 13 Security Council members who voted for the draft that failed on a 13-2 vote.
U.S. Ambassador to the United Nations Susan Rice said Russia and China "will have any future blood spill on their hands." French Ambassador Gerard Araud said the two countries' votes aligned them with a regime that is killing its people.
The Russian and Chinese ambassadors said they support an end to the violence, but disagreed with the text of the resolution, saying it would have complicated the matter and sent mixed signals. Russia and China, which trade with Syria, said they support a dialogue among factions in Syria.