There were no immediate reports of any injuries and no word on the cause of the rapidfire series of spectacular explosions.
Scores of residents were hurriedly evacuated from around the plant as dozens of explosions sent flames more than 100ft into the sky.
Praxair Inc is a global Fortune 500 company and its distribution plant processes propane, gas and oxygen, which is stored in tanks throughout the facility.
Cars catch fire
As the fire spread from one highly flammable tank to another, the explosions shot fiery debris into neighbouring streets where several trucks and cars also caught on fire.
About 70 people work at the plant and the Mayor Francis Slay didn't know "whether foul play was involved or if it was an accident".
The massive explosions set
nearby cars ablaze
The heat from the flames could be felt from blocks away as huge plumes of black smoke spread across the south side of the Missouri city.
The explosions appeared to come from tanks outside the plant, and from the plant itself. Cars and trucks parked nearby caught fire.
Firefighters were forced to stay a block away from the facility where they used ladder-mounted hoses to pour water on one of the densest fires.
Homes and businesses were being evacuated in the mostly residential area south of downtown.
An eyewitness, Angelita Deppe, who works at a nearby United Parcel Service facility that was evacuated by police after the explosions began, said cylinders that had been blasted into the air landed on the ground.
The explosions sent flames more than 150ft in the air.
"It's a highly volatile situation with these gasses on site"
St Louis Mayor
"It's a highly volatile situation with these gasses on site. What they need to do is just let this taking its course, monitor the perimeter and then let it cool down," Mayor Slay said.
Mayor Francis Slay added that the city was monitoring air at the site to make sure no hazardous materials were being released.
One resident said the initial explosion sounded like a bomb had gone off.
"I thought we were being attacked," he told CNN. "The entire five-storey brick building (I was in) shook. It was like a bomb being dropped."