American war correspondent Marie Colvin of Britain's Sunday Times and freelance French photojournalist Remi Ochlik were killed in the city of Homs in what activists said was shelling by President Bashar al-Assad's forces.
Three other Western journalists were wounded in the attack on a makeshift media centre in the Baba Amr district, including Colvin's British photographer colleague Paul Conroy and French reporter Edith Bouvier of Le Figaro.
"This tragic incident is another example of the shameless brutality of the Assad regime," US State Department spokeswoman Victoria Nuland told AFP.
France demanded access to the victims of the attack and summoned Syria's envoy to Paris.
"I am asking the Syrian government to immediately stop attacks and respect its humanitarian obligations," Foreign Minister Alain Juppe said.
"I have asked our embassy in Damascus to require the Syrian authorities provide secure medical access to assist the victims with the support of the International Committee of the Red Cross," he said in a statement.
He said he had also "summoned the Syrian ambassador... to remind him of the intolerable nature of the Syrian government's behaviour."
French President Nicolas Sarkozy said the incident was a further sign that Assad should give up power.
"This shows that enough is enough, this regime must go. There is no reason why Syrians should not have the right to live their lives, to freely choose their destiny," Sarkozy said.
British Prime Minister David Cameron paid tribute to Colvin, saying her death in Syria showed the risks journalists face in exposing the truth.
"This is a desperately sad reminder of the risks that journalists take to inform the world of what is happening and the dreadful events in Syria," Cameron told parliament.
British Foreign Secretary William Hague said Colvin and Ochlik "died bringing us the truth about what is happening to the people of Homs".
"Governments around the world have the responsibility to act upon that truth -- and to redouble our efforts to stop the Assad regime's despicable campaign of terror in Syria," he said.
Russia, which has opposed Western efforts to rein in the Syrian regime, also condemned the deaths.
The foreign ministry said "Moscow resolutely condemns and is seriously concerned" by the killings.
"This tragic event once again confirms the need for all the sides of the Syrian conflict to end the violence and move toward a political course with the start of an all-encompassing national dialogue without preconditions."
Syrian authorities insisted they were not aware Colvin and Ochlik had entered the country and urged foreign reporters in Syria to register with the government.
"The authorities had no information that the two journalists had entered Syrian territory," Information Minister Adnan Mahmud told AFP.
Mahmud said he had asked "specialised authorities in Homs to look for them (Colvin and Ochlik)".
"The ministry urges all foreign journalists who entered Syria illegally to report to the nearest immigration office to legalise their presence," he added.
US-based media tycoon and Sunday Times owner Rupert Murdoch hailed Colvin as one of the best foreign correspondents of her generation.
"It is with great sadness that I have learned of the death of Marie Colvin, one of the most outstanding foreign correspondents of her generation who was killed in Homs in Syria today while reporting for The Sunday Times," Murdoch said in an email to staff.
"Our photographer, Paul Conroy, was with her and is believed to have been injured. We are doing all we can in the face of shelling and sniper fire to get him to safety and to recover Marie's body.
Murdoch said Colvin, who was 56, had "fearlessly" covered conflicts for The Sunday Times for 25 years.
Ochlik, who was 28, was in Syria taking pictures for the IP3 Press agency, which he co-founded in 2005 and for which he had covered previous conflicts including the Arab Spring revolts in Tunisia and Egypt and the conflict in Libya.