The explosion happened at a plant in West, a community north of Waco and south of Dallas.
A Department of Public Safety spokesperson said that between 75 to 100 houses and businesses were completely destroyed in and around the plant.
About 200 people were injured, according to the spokesperson, 40 of them critically. The number of fatalities was unclear, though there are fears the death toll could reach 60 to 70. Officials say at least three of the dead are volunteer firefighters.
The blast registered as a 2.1-magnitude earthquake with the USGS. But seismologists say their sensors can only record the ground motion, and that people who felt the shockwave above ground actually experienced a much larger event.
Department of Public Safety Trooper D.L. Wilson said in a news conference that the town of West is overflowing with people helping.
Wilson said there were confirmed fatalities, but it was not immediately clear how many. Rescue personnel were searching the area for survivors and bodies.
About half the town was being evacuated, according to Wilson. One-hundred-thirty-three people were evacuated from a nearby nursing home.
Wilson said the fire was still smoldering late Wednesday night, preventing firefighters from approaching it.
Authorities set up a staging area on the local high school's football field, which was lit up with floodlights. Ambulances and several dozen injured people could be seen being taken away or seated in wheelchairs as they are treated and await transport.
Department of Public Safety troopers were using their squad cars to transport those injured by the blast and fire at the plant in West, a community north of Waco, Gayle Scarbrough, a spokeswoman for the department's Waco office, told television station KWTX. She said six helicopters were also en route to help out.
The explosion at West Fertilizer was reported shortly before 8 p.m.
A West Fire Department dispatcher told The Associated Press that any casualties would be transported to hospitals in Waco, which is about 90 miles north of Austin.
The explosion knocked out power to many area customers and could be heard and felt for miles around.
The FAA placed a temporary flight restriction over the airspace around the explosion. Only emergency aircraft were allowed to operate. The restriction is standard procedure.
City Hall reportedly sustained significant damage. West Mayor Tommy Muska said at a news conference that there was a fire at the West Fertilizer plant before Wednesday night's explosion.
Muska says he's a volunteer firefighter himself and his helmet was knocked off when the explosion tore through the West Fertilizer plant around 7 p.m. Wednesday.
Muska says the blast badly damaged buildings for a five-block radius around the plant, including a nearby middle school and nursing home. He says the nursing home's 133 residents were safely evacuated.
ABC News and The Associated Press contributed to this report.