A huge explosion happened about 7:50 p.m. local time in the city of West, 320 kilometers north of the Texas capital of Houston.
Dr. George Smith, the head of Texas Emergency Medical Services in West, said at least 60 were dead and some 170 injured.
A fire broke out at the fertilizer plant before the explosion, which devastated surrounding areas, destroying 10 homes and damaging 50 more. It also triggered a 2.1-magnitude earthquake.
Witnesses said an evacuation had already begun before the explosion due to the fire at the plant.
Rescuers launched a door-to-door search overnight in the area near the explosion, looking for dead or injured.
Toxic gas is feared to have been released into the air and authorities are worried that a second fertilizer tank may explode.
The cause of the explosion and the earlier fire in the plant is under investigation.