Arizona Senator Jeff Flake told CNN one person on the lorry was killed by Wednesday morning's impact.
Utah Senator Mike Lee said that the "garbage truck" was "cut in half".
The members of Congress - who included House Speaker Paul Ryan - were on their way to their annual retreat in Greenbrier, West Virginia, when the specially chartered Amtrak train crashed at 11:20 local time (16:20 GMT).
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Some train passengers were hurled from their seats by the collision, which happened near Crozet, Virginia, about 110 miles (180km) south-west of Washington DC.
Jason Lewis, a congressman from Minnesota, was taken to the hospital for a possible concussion, his office said.
"I'm fine compared to, tragically, the truck drivers, and thankful for the prompt action of our doctors and first responders. My thoughts are with the family of the driver who passed away," Mr Lewis said.
Five people were injured when the train struck the lorry, Amtrak spokeswoman Beth K Toll said.
During a meeting at the White House President Trump said, "the train accident was a tough one. A tremendous jolt".
"We don't have a full understanding yet as to what happened but it was a train hitting a truck going at a pretty good speed," he said. "It looks like the driver of the truck was killed, it's very sad to see that."
White House spokeswoman Sarah Sanders said: "There is one confirmed fatality and one serious injury. There are no serious injuries among members of Congress or their staff."
"Senior Administration officials are in regular contact with Amtrak and state and local authorities.
"Our thoughts and prayers are with everyone that has been affected by this incident."
President Donald Trump is due to visit the retreat on Thursday.
Security officials and doctors for the lawmakers - as well as two congressmen who are ex-doctors - helped emergency officials, lawmakers said.
A Michigan congressman said that train passengers had gathered outside the train in prayer.
Tennessee Congressman Chuck Fleischmann said he was walking to the train's toilet when the collision occurred, and he was injured.
"I'm in a bit of shock right now," he told the Tennesseean newspaper. "I'm in a whole lot of pain and discomfort."
Incidents between trains and cars crossing at railway tracks have increased in recent years, according to a report by the Federal Railroad Administration. This is likely due to a higher traffic volume of cars on the road.
Although the cause of the crash is not yet determined, concerns about Amtrak's safety standards have been high after a passenger train in Seattle derailed in December and killed three people.
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