"The Antares rocket suffered an accident shortly after lift-off," NASA mission control in Houston said, describing the blast at Wallops Island, Virginia, as a "catastrophic anomaly."
Orbital's unmanned Cygnus cargo ship was carrying 5,000 pounds (2,200 kilograms) of supplies for the six astronauts living at the research outpost.
After the countdown, the base of the tall, white rocket ignited on cue, then rose a short distance into the air before it suddenly exploded in a fiery blast six seconds later.
Enveloped in flames, the rocket collapsed to the ground, as a cloud of dark gray smoke rose from the wreckage.
Officials said the cost of the rocket and supplies was over $200 million, not including the damage caused on the ground.
Investigators swiftly secured the perimeter of the area and forbade any outside interviews of witnesses or staff, citing classified equipment that had been aboard the spacecraft.