It happened at a crossing on 5th Street (NC-119) around 7:40 a.m.
Witnesses said a flat bed truck was hauling a large excavator used for construction when it got stuck on the tracks as the crossing arms came down.
"He was trying to disconnect his trailer because the train was coming, the gates were coming down," said witness Danny Eldred.
Alamance law enforcement says the driver tried to dislodge the truck, it may have had mechanical problem before it hit the track.
The truck driver was able to get out before the engine of Amtrak train 73 - The Piedmont - slammed into the truck.
"It kind of jolted us forward," said passenger Danielle Baldwin.
"The train just came to a really sudden stop, starting rocking back and forth, and I flew across the back bathroom and hit my head on the metal wall and fell down," said passenger Meagan Eaton.
The truck rolled over several times and the Caterpillar excavator was tossed to the side as the train derailed sparking a fire.
Firefighters used foam to put out the blaze. The force of the crash tore down power lines, trees, and even the crossing arm equipment.
After the crash, the truck driver was seen lying on the ground nearby, but he was not hurt.
"We asked if he was okay. He said 'Yeah.' He was just really concerned about the people on the train," said witness Bob Farrar.
Amtrak said the engine of the train and three passenger cars derailed. There were 36 passengers on board. Twelve had minor injuries. The engineer on the Amtrak train was also taken to the hospital. The wounded went to Duke Hospital in Durham, UNC Hospitals, and Alamance Regional Medical Center.
"The fact that I got out with just a scrape on my head and headache, I think that's really a blessing," said Baldwin.
Firefighters said after the fire that some 1,900 gallons of diesel fuel aboard the train was contained.
About 1,000 gallons of fuel was recovered and officials are trying to clean up any soil contamination, but that will take several days.
Alamance County authorities said the westbound train had just left Durham headed for Greensboro and Charlotte.
Amtrak said the derailment would affect service of trains 76, the Charlotte to Raleigh Piedmont as well as the Carolinian, trains 79 and 80 traveling between New York and Charlotte and Charlotte and New York respectively.
The track was damaged in the crash and will have to be replaced. The rail line will reopen Friday.
The state of North Carolina owns the train that crashed Thursday, but it's operated by Amtrak.
At a mid-morning news conference, investigators said all the safety equipment at the crossing was working and the truck driver should have heeded warning signs prohibiting low vehicles. They said the crossing was not designed for low trucks and said the driver was at fault.
The crash is still under investigation by both state and federal officials.
The truck driver is cooperating with the investigation. Authorities say the driver had a permit to travel the 5th Street route.
Authorities said he is Barry Lazaro of Wake Forest, owner of Lazaro Demolition and Contracting. He did not return calls for comment Thursday.
"We have the signs out and this should not be looked at as a truck route," offered Paul Worley with the North Carolina Department of Transportation.
The train was moving at 70 miles per hour when it hit the truck.
Officials said heavy lifting equipment would be brought in to put the engine and rail cars back on the tracks. They didn't know how long that would take.
Six previous accidents have occurred at the crossing dating back to 1978, including a wreck in 2005 that killed a 78-year-old, according to records from the Federal Railroad Administration. No one was injured in the most recent accident, which occurred in February.