Sunday Times reporter Marie Colvin, an American, and award-winning French photographer Remi Ochlik died when a shell hit a makeshift media centre in the Baba Amr district.
Opposition-held areas of Homs have been besieged since 4 February.
Thousands have died in unrest against the rule of President Bashar al-Assad.
More than 40 people died on Tuesday alone, including Rami al-Sayed, a man who broadcast a live video stream from Homs used by world media.
Mr Sayed was fatally wounded by shrapnel during the shelling of Baba Amr. His brother posted a video of his body in a makeshift hospital.
Ms Colvin and Mr Ochlik were reportedly staying in a house in Baba Amr that was being used by activists as a media centre when it was hit by a shell on Wednesday morning.
Rockets were also said to have hit the building's garden when people tried to flee afterwards.
At least two other foreign journalists were wounded, activists said.
One was named as British freelance photographer Paul Conroy, who was working with Ms Colvin, and Edith Bouvier of the French newspaper, Le Figaro. Ms Bouvier was said to be in a serious condition.
Syrian state television said the information ministry had asked officials in Homs to determine the location of foreign journalists because it had learned that some may have been injured.
In Paris, French Foreign Minister Alain Juppe said the deaths were "another demonstration of the degradation of the situation in Syria and of a repression that is more and more intolerable".
UK Prime Minister David Cameron told parliament: "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."
The US state department referred to "another example of the shameless brutality" of the Syrian regime.
The editor of the Sunday Times, John Witherow, said it was doing what it could to recover Ms Colvin's body and get Mr Conroy to safety.
"Marie was an extraordinary figure in the life of the Sunday Times, driven by a passion to cover wars in the belief that what she did mattered," he added. "She believed profoundly that reporting could curtail the excesses of brutal regimes and make the international community take notice."
There was no immediate comment from Mr Ochlik's agency, IP3 Press.
Mr Ochlik, 28, had reported from Haiti and covered many of the recent uprisings in the Arab world.
Ms Colvin, in her 50s, had been a foreign correspondent for the Sunday Times for two decades, and had reported from several war zones. She lost the sight in one eye in Sri Lanka in 2001 after being hit by shrapnel.
On Tuesday, she told the BBC the bombardment of Baba Amr by Syrian government artillery and tanks had been "unrelenting".
"I watched a little baby die today, absolutely horrific, a two year old - found the shrapnel had gone into the left chest and the doctor said: 'I can't do anything,' and his little tummy just kept heaving until he died. That is happening over and over and over.
"There are 28,000 people in Baba Amr," she added. "The Syrians will not let them out and are shelling all the civilian areas.
The Sunday Times on Wednesday made available Ms Corvin's last article in which she said, "We live in fear of a massacre".
Western journalists have mostly been barred from Syria since the uprising against President Bashar al-Assad began last March.
But increasingly, they have risked entering the country undercover, helped by networks of activists, to report from flashpoints.
Last month, the French television journalist, Gilles Jacquier, was killed in Homs while visiting the city on a government-organised trip.
Anthony Shadid, of the New York Times, died of an apparent asthma attack in Syria last week.
As many as 50 people are feared to have been killed on Tuesday in the northern province of Idlib.
New videos posted online by activists in Idlib suggest opponents of President Assad were the victims of summary executions.