Rights groups say at least five people were shot dead by government troops in the central city of Homs.
Protests were reported in the capital, Damascus, in eastern and western cities and in towns along the border regions.
US Secretary of State Hillary Clinton has warned time is running out for Syria's government to usher in reforms.
Speaking during a visit to Lithuania, she said President Bashar Assad would face more organised resistance to his rule unless the country saw "a genuine transition to democracy".
Human rights groups estimate that about 1,700 people have been killed in three months of anti-government protests.
Mr Assad has promised a dialogue on introducing political reforms but the protesters are calling for him to stand down.
Continue reading the main storyHundreds of thousands are chanting 'Leave, leave, the people want the fall of the regime.' All of Hama is celebrating”End Quote Hama resident 'God, Syria, Bashar' Hundreds of thousands of people were reported to have taken to the streets across Syria after prayers on Friday, following calls on social networks for fresh demonstrations.
Some opposition activists said as many as 3m people joined the demonstrations nationwide, but this figure cannot be independently verified.
In Homs, five people were reportedly shot dead and several injured as government troops fired on protesters - armoured vehicles were deployed in the Baba Amr district of the city, activists said.
Abdel-Karim Rihawi, president of the Syrian League for Human Rights, told AFP news agency tens of thousands of people had left mosques in Deir Ezzor, in the east, and taken to the streets.
Two people were reportedly killed during a protest in Damascus' suburb of Qadam.
Activists said more than 500,000 people were protesting in Hama, 210 km (130 miles) north of Damascus.
Mrs Clinton said she was "hurt" by reports of violence in AleppoOne Hama resident told the BBC Arabic: "Hundreds of thousands are chanting 'Leave, leave, the people want the fall of the regime.' All of Hama is celebrating. There are people chanting from their windows and from the fronts of their homes. All of Hama is on the streets today."
Protests were also staged in Syria's second largest second city of Aleppo, where police fired tear gas against demonstrators, reports say.
Syria's state TV aired images of pro-regime rallies in the northern city.
It showed people waving national flags and chanting "God, Syria, Bashar and that's it."
'Genuine transition'The Syrian Revolution 2011 group had called on protesters to turn out after Friday prayers, with the message to Mr Assad: "We don't love you... Go away, you and your party."
Pro-government rallies were also held in Damascus and several other towns on Friday, with marchers saying they backed Mr Assad's pledges to reform.
The latest anti-Assad demonstrations follow the death of three more civilians overnight in the north-western region of Jabal al-Zawiyah, activists said - two in the town of al-Bara and one in the nearby village of Brim.
AFP also quoted activists as saying there had been explosions on Friday in the coastal city of Latakia.
Speaking earlier on Friday, Mrs Clinton said the Syrian authorities "know what they have to do".
Protests have spread to Aleppo, Syria's second city, activists say "They must begin a genuine transition to democracy and allowing one meeting of the opposition in Damascus is not sufficient action toward achieving that goal," she said.
''It is absolutely clear that the Syrian government is running out of time. There isn't any question about that.
"They are either going to allow a serious political process that will include peaceful protests to take place throughout Syria and engage in a productive dialogue with members of the opposition and civil society, or they're going to continue to see increasingly organised resistance."
Rights campaigners estimate that more than 1,350 civilians and 350 security personnel have been killed since mid-March as security forces try to stifle anti-government protests.
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