The accident occurred about 2 1/2 minutes into the flight from Cape Canaveral, Florida. Pieces could be seen falling into the Atlantic. More than 5,200 pounds of space station cargo were on board, including the first docking port designed for future commercial crew capsules.
"The vehicle has broken up," announced NASA commentator George Diller. He said it was not clear how the disaster occurred or even when the rocket actually failed. Data stopped flowing from the rocket around 2 minutes and 19 seconds, he said. No astronauts were on board.
The California-based SpaceX was trying to figure out what happened, noting that everything appeared to go well in flight until the Falcon 9 rocket went supersonic.
It was a huge setback for NASA, which is counting on private industry to transport cargo - and eventually astronauts - to the orbiting lab. The seven previous SpaceX supply runs had gone exceedingly well.
This is the second failed station shipment in a row. In April, a Russian cargo ship spun out of control and burned up upon re-entry, along with all its precious contents. And last October, another company's supply ship was destroyed in a launch accident.
This Dragon had been carrying replacement food, clothes and science experiments for items lost in those two mishaps.
The three space station residents are in no immediate trouble because of the latest failed delivery. Late last week, NASA's space station program manager, Mike Suffredini, said the outpost had enough supplies on board to make it to October or so.
Russia expects to take another crack at launching supplies on Friday from Kazakhstan.
SpaceX, meanwhile, is one of two companies hired by NASA to start ferrying American astronauts to the space station as early as 2017. The other contender is Boeing.
SpaceX is led by billionaire Elon Musk, who also heads up Tesla, the electric car maker.
Musk has tweeted about the explosion, writing, "Falcon 9 experienced a problem shortly before first stage shutdown. Will provide more info as soon as we review the data."
Falcon 9 experienced a problem shortly before first stage shutdown. Will provide more info as soon as we review the data.— Elon Musk (@elonmusk) June 28, 2015