Seventy-eight passengers and five crew members were aboard when the train moving at more than 80 mph derailed on a route that had raised safety concerns. At least 50 people were hospitalized, more than a dozen with critical or serious injuries, authorities said.
An official briefed on the investigation told The Associated Press that preliminary signs indicate that Train 501 may have struck something before going off the track about 40 miles (64 kilometers) south of Seattle. The official was not authorized to discuss the investigation publicly and spoke on the condition of anonymity.
A local official had raised concerns about the safety of the new bypass as recently as two weeks ago at a public meeting.
The Pierce County Sheriff's Office said several vehicles on Interstate 5 were struck by falling train cars and multiple motorists were injured. No fatalities of motorists were reported.
In a radio transmission immediately after the accident, the train's conductor can be heard saying the train was coming around a corner and was crossing a bridge that passed over Interstate 5 when it derailed.
"I'm still figuring that out. We've got cars everywhere and down onto the highway," he tells the dispatcher, who asks if everyone is OK.
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In a statement, Amtrak said the train that derailed was Train 501, offering service from Seattle to Portland.
The train was making the inaugural run on the new route as part of a $180.7 million project designed to speed up service by removing passenger trains from a route along Puget Sound that's bogged down by curves, single-track tunnels and freight traffic.
The Amtrak Cascades train service is jointly owned by the Washington State Department of Transportation and the Oregon Department of Transportation. Amtrak operates the service for the two states as a contractor and is responsible for day-to-day operations. Amtrak Cascades runs trains from Vancouver, British Columbia, to Eugene, Oregon.
The Amtrak schedule called for the train to leave Seattle around 6 a.m. and arrive in Portland about 3 1/2 hours later.
Monday marked the first public use of the new bypass built on an existing inland rail line that runs along Interstate 5 from Tacoma to DuPont, near where Train 501 derailed. Track testing was completed in January and February in advance of Monday's launch, according to the Washington State Department of Transportation.
The tracks, known as the Point Defiance Bypass, are owned by Sound Transit, the transit agency serving the Seattle area. They were previously owned by BNSF and were used for occasional freight and military transport.
The mayor of Lakewood, Washington, a city along the new route, predicted a deadly crash - but one involving a fast-moving train hitting a car or pedestrian at a grade-crossing, not a train tumbling off an overpass. At a recent public meeting, he called on state planners to build overpass-like rail structures instead of having trains cross busy streets.
The National Transportation Safety Board said a team of investigators was on its way to the scene from Washington, D.C.
The train was going 81.1 mph moments before the derailment, according to transitdocs.com, a website that maps Amtrak train locations and speeds using data from the railroad's train tracker app.
The maximum speed along the stretch of track is 79 mph, according to information about the route posted online by the Washington State Department of Transportation.
All southbound lanes of I-5 were closed south of Joint Base Lewis-McChord, and motorists were being warned to avoid the area.
Associated Press writers Sally Ho and Phuong Le in Seattle, Michael Sisak in Philadelphia, Michael Balsamo in Los Angeles and Gillian Flaccus in Portland contributed to this report.