By 2016, they would have to reach an average of 39 miles per US gallon for passenger cars, and 30 miles per gallon for light lorries.
The new targets would increase the average fuel efficiency of all US cars and light lorries to 35.5 miles per gallon, about 10 miles per gallon more than the current standard.
Announcing the plan at the White House, Mr Obama said the status quo was "no longer acceptable" and led to dependence on oil exporting countries and climate change.
The new standards are expected to raise the price of new vehicles by about $1,300 (£839) per vehicle by 2016.
But the president said this would be offset by lower fuel cost within three years.
UK AND US GALLONS
The UK measurement of a gallon is slightly larger than that for a US gallon.
UK gallon: 4.546 litres
US gallon: 3.785 litres
1 US gallon = 0.833 UK gallons
The US is the biggest car market with more than 250 million cars and light lorries on the road.
The proposed nationwide standard for exhaust emissions is expected to cut the amount of carbon dioxide produced by new passenger vehicles by 34%.
Savings
The Safe Climate Campaign, an environmental group, welcomed the plan saying it was "major signal" that the US was serious about curbing greenhouse gas emissions.
BBC environment analyst Roger Harrabin, in Washington
The president has acted remarkably quickly to come up with a compromise.
It still leaves American fuel efficiency standards lagging behind Europe.
But this is the first American nationwide standard on greenhouse gas emissions - and it will be welcomed by other nations trying to negotiate a new treaty on climate change.
What is interesting is that so far no-one here seems to be protesting.
The AAA drivers association welcome the move for the certainty it gives carmakers and the prospect of lower fuel bills.
They are not complaining at the likely extra purchase price of vehicles.
Carmakers are also hailing a single nationwide standard, after years of court battles to stop California and other states setting their own tough pollution controls.
"GM and the auto industry benefit by having more consistency and certainty to guide our product plans," GM Chief Executive Fritz Henderson said in a statement.
Mr Obama predicted that the lawsuits would be dropped as a result of the proposed regulation.
The president said: "As a result of this agreement we will save 1.8 billion barrels of oil over the lifetime of the vehicles sold in the next five years."
He said this amounted to removing 177 million cars from the roads by 2016.
In that period, the savings in oil will amount to last year's combined US imports from Saudi Arabia, Venezuela, Libya and Nigeria, Mr Obama added.
BBC environment correspondent Richard Black says the plan should act as an incentive for US carmakers to increase fuel efficiency towards European and Asian levels.
The proposed regulation needs the approval of the Environmental Protection Agency and the transportation department.
Bookmark with:
What are these?