The preliminary focus of the probe is speed, officials confirmed.
The NTSB said this afternoon said that preliminary data shows the train exceeded 100 mph before the derailment.
The crash occurred at about 9:28 p.m Tuesday. Six cars overturned and the engine separated from the rest of the train.
What Investigators Are Looking At
Going forward, the NTSB will look at various things: Tracks, train signals, train operation and the train's mechanical condition and human performance, said the NTSB's Robert Sumwalt.
The NTSB has already started to retrieve recorders and get crews' training records, Sumwalt said. However, investigators have not yet carefully documented the wreckage, Sumwalt said, as the search-and-rescue effort "will take precedence over our accident investigation."
"There are many first responders out there," Sumwalt said. "It's a devastating scene."
"We're going to go and very methodically start collecting information -- what was the train speed? What was the speed limit on that curve? That's part of our investigation," Sumwalt said. "To very carefully document that."
The train's black box -- known as an event recorder -- was recovered from the train and is being analyzed at Amtrak's operation center in Delaware, Philadelphia Mayor Michael Nutter said at a news conference today.
"We've just gotten here," Sumwalt added. "You have a lot of questions, we have a lot of questions."
In addition, the NTSB will also look at a forward facing camera at front of engine that “could give us a lot,” Sumwalt said.
Looking forward, Sumwalt said analyzing the event recorders, brake applications, throttle applications, horn and bell will be key to the probe into what happened.
But Nutter said the investigation is ongoing and will take some time. He did not offer an exact timeline.
Deborah Hersman, a former chair of the NTSB, said the investigation will likely include "securing the scene, gathering any perishable evidence and doing a lot of documentation."
According to Hersman, clues like black boxes and possible video cameras may provide investigators with important information.
Investigators will also look at all other trains that traveled the same section of track -- but it's the black boxes that will offer the best clues into what took place, Hersman said.
"The black boxes will tell them things like speed, throttle position, braking. ... But also there are often inward and outward facing video cameras that will tell them a lot of information about the track conditions and the environmental conditions," Hersman said. "The key to the team is going to be grabbing those recorders right away."
Why Is the FBI Involved?
The FBI has also sent agents to the scene who are ready to assist as needed, sources told ABC News.
Given the scale of the derailment and loss of life, the sources say authorities want to identify what caused the derailment as quickly as possible. It's routine for the FBI to be at such a transportation disaster, the sources said.
The Federal Railroad Administration said it was also dispatching at least eight investigators to the scene.
ABC News’ Pierre Thomas contributed to this story.