It was the last regime-held border crossing with Iraq.
The jihadist surge, which has also seen it take Anbar capital Ramadi and the ancient Syrian city of Palmyra in the past week, comes despite eight months of US-led air strikes.
It has sparked an exodus of tens of thousands of civilians in both countries and raised fears IS will repeat at Palmyra the destruction it has already wreaked at ancient sites in Iraq's Nimrud and Mosul.
The United Nations said Friday at least 55,000 people had fled Ramadi alone since mid-May.
President Barack Obama has played down the IS advance as a tactical "setback" and denied the US-led coalition was "losing" to IS.
The Pentagon said on Friday coalition aircraft launched five strikes against IS in Syria and 15 against the jihadists in Iraq in the 24 hours to 0500 GMT.
UNESCO chief Irina Bokova called the 1st and 2nd Century Palmyra ruins "the birthplace of human civilisation", adding: "It belongs to the whole of humanity and I think everyone today should be worried about what is happening."
- A strategic crossroads -
Syria's antiquities director Mamoun Abdulkarim urged the world to "mobilise" to save the treasures at the UNESCO world heritage site with its colonnaded streets, elaborately decorated tombs and temples.
Palmyra is also a strategic crossroads between Damascus and the Iraqi border to the east.
IS executed at least 17 suspected Damascus government loyalists there Thursday, the Syrian Observatory for Human Rights said.
Also on Thursday, a Syrian priest and a colleague were kidnapped from a monastery between Palmyra and Homs, the French NGO L'Oeuvre d'Orient said.
Father Jacques Mourad, who was known to help both Christians and Muslims, was preparing aid for an influx of refugees from Palmyra.
IS now controls "more than 95,000 square kilometres (38,000 square miles) in Syria, which is 50 percent of the country's territory," the Observatory said.
Matthew Henman, head of IHS Jane's Terrorism and Insurgency Centre, said the jihadist advance "reinforces IS's position as the single opposition group that controls the most territory in Syria".
According to the Observatory, IS gains mean a mere 22 percent of Syria's territory is still in regime hands.
Syria's opposition government in exile said the regime controlled "less than a quarter" of the country.
IS's jihadist rival, Al-Qaeda affiliate Al-Nusra Front, has also been on the offensive as part of a rebel alliance that has stormed through nearly all of the northwestern province of Idlib.
- Saudi mosque attacked -
On Friday, the alliance overran a hospital in Jisr al-Shughur where at least 150 regime forces and dozens of civilians were trapped for nearly a month, the Observatory said.
Dozens managed to escape but despite a pledge from President Bashar al-Assad to rescue them, others were killed, it said.
The Observatory also reported eight women and three young girls killed by regime barrel bombs in the northern province of Aleppo.
In Saudi Arabia's Eastern Province, a suicide bomber attacked a Shiite mosque, killing and wounding several people, authorities said.
IS said it was behind the attack, the first time the group has officially claimed an attack in the oil-rich kingdom.
A jihadist statement online warned of "dark days ahead" for Shiites until militants "chase them from the Arabian Peninsula".
The blast and Palmyra's takeover came just days after IS seized the Iraqi city of Ramadi, their most significant victory since last summer's lightning advance across swathes of northern Iraq.
Officials said IS also seized Iraqi positions east of Ramadi on Thursday, but added that government forces were preparing a counteroffensive "in the coming days".
Iraqi forces cleared a ground route to the country's largest oil refinery at Baiji, under siege by IS for months, the US military said on Friday.
Obama blamed the fall of Ramadi on a lack of training and reinforcements for its garrison, saying Iraqi security forces in "Sunni parts of the country" needed speedier support.
Iraqi Deputy Prime Minister Saleh Mutlaq, a leading Sunni Arab, called for a change of US strategy.
Recruiting Sunni tribes is "important but not enough," he said, adding that in any case it was "too late".