The Francis Scott Key Bridge in Baltimore collapsed after a container ship ran into it.
Media reports said that the vessel crashed into the bridge at about 1:30am on Tuesday, catching fire before sinking.
At least seven people and seven vehicles are said to have fallen into the water.
Officials have called the incident a “developing mass casualty event”.
Multiple vehicles were on the bridge at the time, including one the size of a tractor-trailer.
Kevin Cartwright, director of communications for the Baltimore Fire Department, has said emergency responders were searching for at least seven people believed to be in the water.
He said agencies received 911 calls at about 1:30am reporting a vessel travelling outbound from Baltimore had struck a column on the bridge, causing it to collapse.
“Our focus right now is trying to rescue and recover these people,” Cartwright told AP.
According to ship tracking data, a Singapore-flagged container ship, Dali, was along the bridge where the accident occurred.
The registered owner of the ship is Grace Ocean Pte Ltd and the manager is Synergy Marine Group
Synergy Marine Group has issued a statement on the ship’s collision with a pillar of the Francis Scott Key Bridge in Baltimore.
The company said all crew members, including the two pilots, had been accounted for and there were no reports of any injuries.
“Whilst the exact cause of the incident is yet to be determined, the ‘Dali’ has now mobilized its Qualified Individual Incident response service,” the statement added
Kevin Cartwright, of the Baltimore Fire Department, says up to 20 people are feared to be in the water after the collapse of the bridge.
“We understand up to 20 individuals may be in the Patapsco River right now as well as multiple vehicles,” he told CNN, saying officials were dealing with a “mass casualty multi-agency incident”.
The 2.6km (1.6-mile), four-lane bridge spans the Patapsco River just southeast of central Baltimore.
It opened in 1977 and carries more than 11 million vehicles annually.
It is a major part of the road network around Baltimore, an industrial city on the US East Coast northeast of the capital, Washington, DC.