The town of West, near Waco, has been evacuated amid fears of poison fumes spewing from the plant. Officials say between 50 and 70 homes have been damaged, along with a large apartment building. A nursing home with over 100 residents is believed to have collapsed.
US media are reporting two emergency service workers, called to a blaze at the plant before the explosion, are dead and others are unaccounted for. Officials have confirmed fatalities, but not the toll.
Ammonia-filled gas clouds are preventing people getting within 5km of the blast and making search and rescue efforts difficult.
The explosion was so big that it registered on state earthquake recorders as magnitude 2.1 seismic event.
CNN reported that hospitals had been told to expect "somewhere in the neighbourhood" of 100 people injured. A field triage centre had been set up.
Hospitals in the area have had "a steady flow" of people being admitted with orthopaedic injures and major blood loss.
Glenn A Robinson, the chief executive of Hillcrest Baptist Medical Center in Waco, told CNN that his hospital had received 66 injured people for treatment, including 38 who were seriously hurt.
He said the injuries included blast injuries, orthopedic injuries, large wounds and a lot of cuts. The hospital has set up a hotline for families of the victims to get information, he said.