"I strongly condemn the violence that has erupted in Cairo and throughout Egypt," Ashton said in a statement, adding that the violence left Egypt "heading into an uncertain future".
"I call on the security forces to exercise utmost restraint and on the interim government to end the state of emergency as soon as possible, to allow the resumption of normal life," she said.
U.S. Secretary of State John Kerry and U.N. Secretary-General Ban Ki-moon also deplored the use of force and called for the state of emergency to be lifted as soon as possible.
Egyptian security forces crushed the protest camps of thousands of supporters of the deposed Islamist president on Wednesday, shooting almost 200 of them dead in the bloodiest day in decades and polarising the Arab world's most populous nation.
At least 235 people were killed in all, including at least 43 police, and 2,000 wounded, a health official said, in fierce clashes that spread beyond Cairo to towns and cities around Egypt. Deposed president Mohamed Mursi's Muslim Brotherhood said the death toll of what it called a "massacre" was far higher.
While bodies wrapped in carpets were carried to a makeshift morgue near the Rabaa al-Adawiya mosque, the army-backed rulers declared a one-month state of emergency, restoring to the military the unfettered power it wielded for decades before a pro-democracy uprising toppled autocrat Hosni Mubarak in 2011.
Interior Minister Mohamed Ibrahim said 43 police were among the dead. Security forces had completely cleared two protest camps in the capital and would not tolerate any further sit-ins, he said, vowing to restore Mubarak-era security.
Prime Minister Hazem el-Beblawi defended the use of force, condemned by the United States and European governments, saying the authorities had no choice but to act to end "the spread of anarchy".
"We found that matters had reached a point that no self-respecting state could accept," he said in a televised address.
The authorities imposed a dusk-to-dawn curfew in Cairo and several other cities including Alexandria, Egypt's second city on the Mediterranean coast.
The use of force prompted Mohamed ElBaradei, a former U.N. diplomat and the most prominent liberal supporter of Mursi's overthrow, to resign as vice president, saying the conflict could have been resolved by peaceful means.
Thousands of Mursi's supporters had been camped at two major sites in Cairo since before he was toppled on 3 July, and had vowed not to leave the streets until he was returned to power.
Violence rippled out from Cairo, with Mursi supporters and security forces clashing in the cities of Alexandria, Minya, assiut, Fayoum and Suez and in Buhayra and Beni Suef provinces.
The bloodshed also effectively ended for now the open political role of the Brotherhood, with the harshest crackdown on a movement that survived underground for 85 years to emerge after the 2011 uprising and win every election held since.
Security officials initially said senior Brotherhood figures Mohamed El-Beltagi and Essam El-Erian had been arrested, joining Mursi himself and other Brotherhood leaders in jail, but later acknowledged they had not been captured. Beltagi's 17-year-old daughter was among the dead.
Beltagi warned of wider conflict, and urged people to take to the streets to oppose the head of the armed forces, who deposed Mursi on July 3 following mass protests.
"I swear by God that if you stay in your homes, Abdel Fattah al-Sisi will embroil this country so that it becomes Syria. Abdel Fattah al-Sisi will push this nation to a civil war so that he escapes the gallows."
ElBaradei's political movement, the anti-Islamist National Salvation Front, did not share his qualms, declaring that "Egypt has held its head high in the sky announcing victory over political groups that abuse religion".
The violence was the worst in Egypt since war with Israel in 1973 and forces tough decisions upon Egypt's Western allies, especially Washington, which funds Egypt's military with $1.5 billion a year and has so far refused to label the army's overthrow of Mursi a "coup".
The United States and Europe had pressed hard for Egypt's generals not to crush the demonstrators. A diplomatic effort to open talks between the Brotherhood and the authorities, backed by Washington, Brussels and Arab states, collapsed last week.
Outside of Cairo, state media said Mursi supporters had besieged and set fire to government buildings and attacked several churches. Christians, who make up 10% of the population of 85 million, have feared reprisals from Islamists since the Coptic Pope Tawadros endorsed the military takeover.
Among the dead in Cairo were at least two journalists. A Reuters photographer was shot in the foot.
At a makeshift morgue at the camp field hospital, a Reuters reporter counted 29 bodies, with others still arriving. Most had died of gunshot wounds to the head.
Adli Mansour, the judge appointed president by the army when it overthrew Egypt's first elected leader on 3 July, announced a state of emergency for one month and called on the armed forces to help police enforce security. Rights activists said the move would give legal cover for the army to make arrests.
Turkey urged the U.N. Security Council and Arab League to act quickly to stop a "massacre" in Egypt. Iran warned of the risk of civil war.