Friday's demonstrations were a response to a call by the Facebook group Syrian Revolution 2011, a driving force behind three months of protests against the autocratic rule of President Bashar al-Assad.
Five people died in Damascus, another five in the town of Kiswah south of the capital, three in Homs and two others near the central city, activists told AFP.
"Security forces tried to break up a rally calling for the fall of the regime with tear gas before opening fire," killing five and wounding 25 others, said an activist in the Damascus neighbourhood of Barzeh.
Activists said dozens of people in Barzeh were arrested in house-to-house searches and a curfew was also imposed there, although it was not clear when it would be lifted.
"Demonstrators left the mosque after Friday prayers and marched for a few minutes until security forces opened fire to disperse them, killing five people and wounding six others," said Mohammad Enad Suleiman.
Three people were killed in Homs and two others near the central city when security forces opened fire on protesters, according to activists at the scene.
Demonstrations rocked many other cities, including the eastern oil hub of Deir Ezzor where 30,000 protesters filled the streets, said Rami Abdel Rahman of the London-based Syrian Observatory for Human Rights.
Security forces also arrested between 70 and 80 protestors in Mareh near Aleppo, Syria's largest city, after anti-government protests, activists said.
State television blamed the civilian deaths in Barzeh on "armed men," saying they also wounded several security force members including an officer.
It added that a police officer was also shot dead in the Damascus suburb of Kadam, and the official SANA news agency reported that "several members of the security forces were hit by gunfire in Kiswah."
Syria blames the violence on "armed terrorist gangs" and says the protests are being orchestrated from abroad.
Syrian rights groups say that more than 1,300 people have been killed and 10,000 have been arrested in the regime's brutal crackdown on dissent since the protests erupted on March 15.
The latest protests were held under the slogan "Fall of legitimacy," with a Facebook page message reading: "Bashar is no longer my president and his government no longer represents me."
The crackdown has sent nearly 12,000 Syrians fleeing to safety in neighbouring Turkey, prompting US Secretary of State Hillary Clinton to warn of the risk of regional escalation.
The European Union scorned Assad's regime, saying its legitimacy was undermined by the crackdown.
A declaration adopted at an EU summit in Brussels "condemns in the strongest possible terms the ongoing repression and unacceptable and shocking violence the Syrian regime continues to apply against its own citizens.
"By choosing a path of repression instead of fulfilling its own promises on broad reforms, the regime is calling its legitimacy into question," it added, saying all those responsible for targeting civilians would be held accountable.
The EU leaders also urged the UN Security Council to adopt a resolution condemning the crackdown, a move opposed by veto-wielding member Russia.
Earlier this week, the EU slapped fresh sanctions on Syria, expanding a blacklist targeting 23 top leaders including the embattled Assad and three commanders of Iran's Revolutionary Guard accused of aiding the crackdown.
Damascus reacted angrily to the sanctions, with Foreign Minister Walid Muallem saying they were "equivalent to war" and denying receiving Iranian help.
Meanwhile, the number of Syrians sheltering in Turkey has approached 12,000 after some 1,500 refugees poured across the border on Thursday and Friday, officials in Ankara said.
Clinton said the Syrian troop buildup was "worrisome," could increase the chances of a border clash and "only exacerbate the already unstable refugee situation in Syria."
The EU declaration called for "maximum restraint" following Syrian military activity near the Turkish border.
"What is happening in Syria is quite appalling, thousands of people are being killed, tens of thousands have been interned," British Prime Minister David Cameron said.