The US Coast Guard has described it as a "very serious spill"
Robotic submersibles are being used to try to stop oil leaking into the Gulf of Mexico from a damaged well almost a mile (1.5km) below the surface.
Some 1,000 barrels (42,000 gallons) of oil a day have been gushing from the well since a drilling rig exploded and sank off the Louisiana coast last week.
British oil company BP, which leased the rig, said the "first-of-its-kind" attempt would take 24 to 36 hours.
A nearby oil platform has been evacuated as a precaution.
Workers on the rig, the Ocean Endeavour, were taken away because the oil slick was coming dangerously close, said the US Minerals Management Service.
Conservation experts say the oil has the potential to damage beaches, barrier islands, wetlands and wildlife reserves along hundreds of miles of coastline in four US states.
Whales have been spotted near the spill but they did not appear to be in distress.
For now, the weather conditions are keeping the oil away from the shore and it is hoped the waves will break up the heavy crude oil, allowing it to harden and sink back to the ocean floor.
The oil is not expected to reach land for at least another three days.
Officials are monitoring the environmental effects by boat and plane.
BP - which is responsible under federal law for the clean-up - said it was using four submersible vehicles, equipped with cameras and remote-controlled arms, to try to activate a blow-out preventer - a series of pipes and valves that could stop the leak.
OIL SPILL DISASTERS
1991: 520m gallons were deliberately released from Iraqi oil tankers during the first Gulf War to impede the US invasion
1979: 140m gallons were spilt over nine months after a well blow-out in the Bay of Campeche off Mexico's coast
1979: 90m gallons leaked from a Greek oil tanker after it collided with another ship off the coast of Trinidad
1983: 80m gallons leaked into the Gulf over several months after a tanker collided with a drilling platform
1989: 11m gallons were spilt into Alaska's Prince William Sound in the Exxon Valdez disaster
However, this was a "highly complex task" and "it may not be successful", said chief operating officer of BP's exploration and production unit, Doug Suttles.
If the blow-out preventer does not seal off the well, the company intends to place a large dome directly over the leaks to catch the oil and send it up to the surface, where it could be collected by ships.
This has been done before, but only in shallow waters, Mr Suttles said.
Another alternative is to drill a "relief well" intersecting the original well, but he warned that this might take two to three months to stop the flow.
BP has brought in more than 30 clean-up vessels and several aircraft to spray dispersant on the oil floating on the surface.
Bad weather forced the operation to be suspended at the weekend.
In that time, the oil slick was estimated to have grown to about 600 sq miles (1,550 sq km), officials said.
The US Coast Guard has described it as a "very serious spill".
Coast Guard Petty Officer Connie Terrell said 32 vessels were waiting for conditions to improve to resume the clean-up.
She could not say when they would be back at work, but said 23,000ft (7km) of containment booms had been deployed, 70,000ft more were ready to go when the effort resumed, and another 50,000ft were on order.
The Deepwater Horizon burned for 36 hours before it sank on Thursday.
It had been carrying out exploratory drilling 52 miles south-east of Venice, Louisiana, when the blast occurred.
Eleven workers are still missing and presumed dead. The search for them has been called off.
Another 126 workers were rescued.
An investigation into the cause of last Tuesday's explosion is continuing.
In 2009, BP was fined a record $87m (£53m) for failing to improve safety conditions following a massive explosion that killed 15 people at its Texas City refinery.
The US Mineral Management Services found no violations on the Deepwater Horizon rig when it carried out routine inspections in February, March and April this year.
The current leak would have to continue for more than eight months to match the 11m-gallon spill from the oil tanker Exxon Valdez off Alaska in 1989, the worst oil spill in US history.