The Amtrak train car fell from an overpass, landing on the I-5 highway outside Seattle. All lanes of traffic have been closed.
Authorities have not yet confirmed the extent of casualties. But witnesses say several people have been injured.
Local news stations report that this was the inaugural run of the new high-speed rail line.
The crash occurred around 07:30 (15:30 GMT), about 45 minutes into train 501’s journey between Portland and Seattle.
Before the crash, it was travelling at more than 80mph (130kmh).