Obama signed the executive order to "increase pressure on the government of Syria to end its use of violence and begin transitioning to a democratic system that ensures the universal rights of the Syrian people," the document said.
The order targets Vice President Faruq al-Shara, Prime Minister Adel Safar, Interior Minister Mohammed Ibrahim al-Shaar, Defense Minister Ali Habib Mahmud, Military Intelligence Chief Abdul Fatah Qudsiya, and Mohammed Dib Zaitoun, director of Political Security Directorate.
The sanctions block any property the seven have in the United States or any "in the possession or control of US persons in which the designated individuals have an interest," the document distributed by the State Department said.
In imposing the sanctions, the Obama administration stopped short of saying Assad had lost his legitimacy to rule, a formula Washington has applied to Libyan leader Moamer Kadhafi whose forces are engaged in a war with rebels.
"We are saying that we oppose his behavior and that he needs to stop his policies of repression and mass arrests and begin a political transition that ensures fair representation and democratic rights for Syrians," the document said.
"We are also saying that Assad is isolating himself from the international community due to his egregious actions," it said.
"It is up to Assad to lead a political transition or to leave," it added.
Assad had been spared sanctions until now, two months into the protests that were inspired by other pro-democracy movements sweeping the Arab world, including those that have ousted the Egyptian and Tunisian leaders.
On April 30, Obama imposed asset freezes and restrictions on financial transactions, notably against Maher Al-Assad, the powerful brother of the president, who commands Syria''s feared Fourth Armored Division.
Also named in Obama's executive order enshrining the sanctions were Ali Mamluk, director of Syria's Intelligence Directorate, and Atif Najib, the ex-head of intelligence in Daraa province, the epicenter of the recent political violence.
Syrian forces were accused of killing at least eight more people on Wednesday in the besieged border town of Tall Kalakh, according to human rights activists.
More than 850 people are believed to have been killed and another 8,000 arrested since anti-regime protests erupted two months ago, according to rights watchdogs.