The US has stepped up its sanctions on Iran for "supporting terrorists" and pursuing nuclear activities.
The guards force was established after the Islamic revolution in 1979
The new measures target the finances of Iran's Islamic Revolution Guards Corps and three state-owned banks.
US Secretary of State Condoleezza Rice said the moves were part of "a comprehensive policy to confront the threatening behaviour of the Iranians".
But Iran said the latest "hostile policies" were counter to international law, and accused the US of hypocrisy.
The US declared the Revolutionary Guards a "proliferator of weapons of mass destruction", a reference to ballistic missiles they are allegedly developing, while their elite overseas operations arm, the Quds Force, was singled out as a "supporter of terrorism".
The US has repeatedly accused Iran of destabilising Iraq and Afghanistan, blaming the Revolutionary Guards for supplying and training insurgents.
Ms Rice accused Iran of a litany of abuses, including pursuing technologies "that can lead to a nuclear weapon", building ballistic missiles, and spurning peace talks.
She said Iran was supporting militants in Iraq and "terrorists" in Iraq, Afghanistan, Lebanon and the Palestinian territories, and said Iran had threatened to destroy Israel.
Officially the Islamic Revolution Guards Corps (IRGC), or Pasdaran
Formed after 1979 revolution
Loyal to clerics and counter to regular military
Estimated 125,000 troops
Includes ground forces, navy, air force, intelligence and special forces
Also has political influence: dozens of ex-guard sit as MPs
Iran President Ahmadinejad is a former member
Under Executive Order 13382, US authorities will be able to freeze the assets of, and prohibit any US citizen or organisation from doing business with the Revolutionary Guards.
Iran's ministry of defence, which controls the country's defence industry, three Iranian banks, and several companies owned by the Guards will also be designated.
The Revolutionary Guards corps has widespread business interests including car factories, newspapers and oil and gas fields.
"These actions will help to protect the international financial system from the illicit activities of the Iranian government," Ms Rice said.
The British government said it "endorsed" the move, but it was condemned by Iran's foreign ministry.
"The hostile policies of America against the respectful Iranian nation and our legal organisations are against international regulations and have no value," the state broadcaster IRIB quoted a spokesman as saying.
"It is incongruent for a country who itself is a producer of weapons of mass destruction to take such a decision. A country that has created and supported many terrorist groups cannot obstruct the course of development, progress and prosperity for the Iranian nation," said Mohammad Ali Hosseini.
Ms Rice has reiterated a commitment to finding a diplomatic resolution to the crisis and has offered to meet "my Iranian counterpart any time, anywhere" - words that would be unimaginable coming from the lips of Vice-President Dick Cheney, says the BBC's Justin Webb in Washington.
Mr Cheney is widely believed to be pressing for a military strike on Iran before the Bush administration's term is over, our correspondent says.
If these sanctions have no effect, Ms Rice may well have to give way to those in and around the White House who believe the time for diplomacy is over, he says.
Last month the US Senate voted to designate the entire Revolutionary Guard a terrorist organisation, but Thursday's announcement does not go that far.
The designation of "global terrorist group" is instead reserved for its foreign arm, the Quds Brigade, which has been accused by US officials of supplying powerful roadside bombs and rocket-propelled grenades to Shia militants in Iraq.
Thought to have 15,000 troops, it is responsible for conducting covert missions overseas and for forging relationships with other Shia groups.
"The Quds Force controls the policy for Iraq," the top US military commander in Iraq, Gen David Petraeus, said earlier this month. "There should be no confusion about that."