Emergency responders at the site of a fatal collision between an Amtrak passenger train and a CSX freight train near Cayce, S.C., on Sunday. Lexington County Sheriff's Department, via Associated Press

An Amtrak train traveling from New York to Miami collided with a freight train early Sunday, killing at least two people, injuring at least 70 others and spilling thousands of gallons of fuel, according to officials.

Amtrak said Train 91, which was carrying eight crew members and 139 passengers, collided with a CSX train near Cayce, S.C., around 2:35 a.m.

“The lead engine derailed, as well as some passenger cars,” Amtrak said in a statement.

The Lexington County spokesman, Harrison Cahill, said at a news conference early Sunday that about 70 people with injuries had been hospitalized. He said the injuries ranged from small scratches and bumps to broken bones, but could not say if any were life-threatening.

It was the second major crash involving an Amtrak train in less than a week. On Wednesday, a train carrying Republican members of Congress to a retreat in West Virginia hit a garbage truck in rural Virginia, killing a passenger in the truck.

The cause of the crash on Sunday was not immediately clear. The National Transportation Safety Board said on Twitter that investigators were on their way to the collision site.

The train, operating Amtrak’s Silver Star service, originated at Pennsylvania Station in New York and was bound for Miami. The Lexington Sheriff’s Department said on Twitter that the crash occurred near Charleston Highway and Pine Ridge Road close to Pine Ridge, S.C.

All passengers have been removed from the train, officials said. Capt. Adam Myrick of the Lexington Sheriff’s Department said that the uninjured had been taken to a Red Cross reception site.

“We know that they are shaken up quite a bit,” he said. “We know that this is unlike anything else that they have ever been through, so we wanted to get them out of the cold, get them out of the weather, get them to a warm place.”

The Red Cross said on Twitter that “disaster trained volunteers” were responding to the accident.

Mr. Cahill said a hazardous materials team had been called to the site because roughly 5,000 gallons of fuel had spilled as a result of the collision.

“We were able to secure two leaks of fuel from the trains,” he said, adding there was “no threat to the public at this time.”

“This is not our first train derailment,” said Derrec Becker of the South Carolina Emergency Management Division, citing a fatal derailment in January 2005. A 42-car freight train operated by Norfolk Southern crashed into a smaller train near Granitteville, S.C., killing eight people, injuring more than 200 and leaking chlorine gas.

“It’s unfortunate that we have two fatalities,” he said of the crash on Sunday. “Our hearts are with those families right now.”

Senator Tim E. Scott, Republican of South Carolina, also expressed his condolences on Twitter to the families of those killed and those injured.

Derek Pettaway, a passenger on the train, told CNN that he had been asleep at the time of the crash, but that officials reacted swiftly and passengers were led off quickly.

“Nobody was panicking, people were in shock more than anything,” he said, according to The State’s website.

He said it was too dark to see much, but most of the cars he glimpsed ended up off the tracks but upright.

Amtrak has had a number of high-profile crashes and derailment over the years, leading to criticism from consumer advocates and government officials. Federal Railroad Administration statistics have shown that in recent years the agency has had an average of about two derailments a month, accounting for about one-quarter of all the accidents it reports.

Most derailments, however, have rarely caused more than minor injuries.

Amtrak maintains that it has been a “safe and reliable transporter of more than 30 million passengers” and that it has a strong safety record. However, after a train hit a piece of track equipment and derailed, killing two, it said in a statement, “We need to assess how we can get better.”

Amtrak has also installed technology known as positive train control on parts of its rail network in the Northeast Corridor after passenger trains traveling well above the speed limit derailed, leaving a trail of death and injuries.

In the Amtrak crash in Virginia on Wednesday, two passengers from the truck were injured — one seriously — and hospitalized. Two members of the train’s crew and at least two passengers, including Representative Jason Lewis, Republican of Minnesota, were also hospitalized with minor injuries.

Republicans had chartered the train to carry them from Washington to the Greenbrier resort in West Virginia, where the party was holding its annual policy retreat. Several lawmakers who were on the train estimated that more than half of the Republican members of the House and Senate, including Speaker Paul D. Ryan, were on board, and that many were accompanied by their spouses.

In December, a passenger train on a newly opened Amtrak route jumped the tracks on an overpass south of Tacoma, Wash., slamming rail cars into a busy highway, killing at least three people and injuring about 100 others.

In 2015, an Amtrak train derailed in Philadelphia, killing eight people and injuring more than 200. A Pennsylvania judge dismissed involuntary manslaughter charges against the Amtrak engineer, saying it appeared to be an accident and not the result of criminal negligence.

After the crash on Sunday, Amtrak posted on Twitter: “Individuals with questions regarding passengers on train 91 can contact us at 1.800.523.910.”