The United States immediately warned Americans to stay away from all U.S. diplomatic facilities in Turkey and to be wary in large crowds.
The blast drew condemnation from Turkey, the U.S., Britain and other nations and officials from both Turkey and the U.S. pledged to work together to fight terrorism.
"A suicide bombing on the perimeter of an embassy is by definition an act of terror. It is a terrorist attack," White House spokesman Jay Carney.
Turkish Prime Minister Recep Tayyip Erdogan said police believe the bomber was connected to a domestic leftist militant group. Carney, however, said the motive for the attack and who was behind it was not known.
A respected Turkish television journalist was also seriously wounded in the 1:15 p.m. blast in the Turkish capital and two other guards sustained lighter wounds, officials said.
The state-run Anadolu Agency identified the bomber by his first name and initial – Ecevit S. It said the 40-year-old man was a member of the outlawed Revolutionary People's Liberation Party-Front, or DHKP-C, which has claimed responsibility for assassinations and bombings since the 1970s.
The group has been designated a terrorist organization by the United States but had been relatively quiet in recent years.
The U.S. Embassy building in Ankara is heavily protected and located near several other embassies, including those of Germany and France.
Friday's explosion occurred inside the security checkpoint at the side entrance to the U.S. embassy, which is used by staff. A guard standing outside the checkpoint was killed while the two guards that were wounded "were standing in a more protected area," said Interior Minister Muammer Guler said.
The two were treated on the scene and did not require hospital treatment, he said.
The Hurriyet newspaper said staff at the embassy took shelter in "safe room" inside the compound soon after the explosion.
Police swarmed the area and immediately cordoned it off. Forensic investigators in white outfits and gloves soon combed the site.
TV footage showed the embassy door blown off its hinges. The blast also shattered the windows of nearby businesses, littering debris on the ground and across the road. The inside of the embassy did not appear to be damaged.
Television footage also showed what appeared to be a U.S. marksman in a helmet and body armor surveying the area from�the roof of an embassy building.
In a statement, the U.S. Embassy thanked Turkey for "its solidarity and outrage over the incident."
U.S. Ambassador Francis Ricciardone declared that the U.S. and Turkey "will continue to fight terrorism together" and described the U.S. Embassy compound as secure.
"From today's event, it is clear that we both suffer from this terrible, terrible problem of today's world. We are determined after events like this even more to cooperate together until we defeat this problem together," he said.
Erdogan echoed that sentiment, saying the attack aimed to disturb Turkey's "peace and prosperity" and demonstrated a need for international cooperation against terrorism.
"We will stand firm and we will overcome this together," he said.
In Washington, State Department spokeswoman Victoria Nuland said U.S. officials were "working closely with the Turkish national police to make a full assessment of the damage and the casualties, and to begin an investigation."
Carey, the White House spokesman, said the attack would strengthen Turkey and the United States' "resolve."
"Turkey remains one of our strongest partners in the region, a NATO ally," he said. "We have worked shoulder-to-shoulder with the Turks to counter terror threats ... and this will only strengthen our resolve. Turkey has been a very important ally, broadly speaking and in the effort to counter terrorism."
Foreign Minister Ahmet Davutoglu vowed that Turkey would spare no effort in protecting diplomatic facilities.
"We have always shown great sensitivity to the protection of foreign missions and we will continue to do so," he said.
The injured journalist was 38-year-old Didem Tuncay, who until recently had worked for NTV television. A hospital official said she was "not in critical condition."
Ricciardone visited Tuncay in the hospital and told reporters outside that he had invited her to the U.S. Embassy for tea.
He also paid tribute to the Turkish guard who was killed, calling him a "Turkish hero" who died while defending U.S. and Turkish staff at the Embassy.
Americans in Turkey were warned to avoid visiting the embassy or U.S. consulates in Istanbul and Adana until further notice and were told to register on the State Department's website.
"The Department of State advises U.S. citizens traveling or residing in Turkey to be alert to the potential for violence, to avoid those areas where disturbances have occurred, and to avoid demonstrations and large gatherings," the U.S. Consulate in Istanbul said in a statement.
British Foreign Secretary William Hague condemned Friday's attack "in the strongest terms" and said Turkey and the U.S. will get the U.K.'s full support as they seek to hold those responsible to account.
Israeli Prime Minister Benjamin Netanyahu sent a message to President Barack Obama saying he was "shocked and saddened to learn of the vicious terrorist attack."
U.S. diplomatic facilities in Turkey have been targeted previously by terrorists. In 2008, an attack blamed on al-Qaida-affiliated militants outside the U.S. Consulate in Istanbul left three assailants and three policemen dead.
Elsewhere, terrorists attacked a U.S. mission in Benghazi, Libya, on Sept. 11 last year, killing U.S. Ambassador Chris Stevens and three other Americans. The attackers in Libya were suspected to have ties to Islamist extremists, and one is in custody in Egypt.
Turkey's parliament speaker, Cemil Cicek, linked Friday's attack to the arrest last month of nine Turkish human rights lawyers, who prosecutors have accused of links to the DHKP-C.
"There was an operation against this organization," Cicek said and suggested the attack could be an attempt by the group to "say `We are still here, we are alive.'"
In past years, the DHKP-C group has spearheaded hunger strikes against Turkish prison conditions that led to the deaths of dozens of inmates. The protesters opposed a maximum security system in which prisoners were incarcerated small cells instead of large wards.
In September, police said a leftist militant threw a hand grenade and then blew himself up outside a police station in Istanbul, killing a police officer and injuring seven others. Police identified the bomber as a member of the DHKP-C.
In 2008, Turkish police said they had foiled a bomb plot by DHKP-C against some U.S. companies in Turkey.
Turkey has also seen attacks linked to homegrown Islamic militants tied to al-Qaida. In a 2003 attack on the British consulate in Istanbul, a suspected Islamic militant rammed an explosive-laden pickup truck into the main gate, killing 58 people, including the British consul-general.
Associated Press writers Ezgi Akin in Ankara, Turkey, Christopher Torchia in Istanbul and Cassandra Vinograd in London contributed to the report.