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This is the first time there has been an accident on landing in the 42 years of American space flight.
President George Bush told a nation in shock: "The Columbia is lost. There are no survivors."
Six of the seven astronauts were US citizens. They were Rick Husband, William McCool, Michael Anderson, David Brown, and female astronauts Laurel Clark and Indian-born Kalpana Chawla.
The seventh - fighter pilot Colonel Ilan Ramon - was Israel's first astronaut and was carrying with him a miniature Torah scroll of a Holocaust survivor.
Columbia disintegrated just 16 minutes before it was due to land at Cape Canaveral in Florida.
At 0900 local time (1400 GMT) Mission Control lost all data and contact with the crew.
The US space agency Nasa then sent search teams to the Dallas-Fort Worth area amid reports of "a big bang" and TV pictures showing smoke and fireballs in the sky.
Debris scattered over Texas
In an emotional announcement, Nasa's administrator Sean O'Keefe, said: "This is indeed a tragic day for the Nasa family, for the families of the astronauts and likewise, tragic for the nation."
Flags at the Kennedy Space Center have been lowered to half-mast.
Debris from the shuttle is scattered across eastern Texas and western Louisiana and has crashed into car parks, forests, backyards, a reservoir, a rooftop and a dentist's office.
Nasa has temporarily suspended shuttle flights. Shuttle programme manager Ron Dittemore told a news conference in Houston, Texas, "We will not fly again until we have this understood. Somewhere along the line we missed something."
The finger of blame points to a piece of insulating foam from an external fuel tank that hit the shuttle's left wing as it took off 16 days ago.
Some experts say this could have damaged tiles that protect the craft from intense heat on re-entry into the Earth's atmosphere.
But the lead flight director in mission control, Leroy Cain, assured journalists engineers had concluded any damage to the spacecraft was considered minor.
The shuttle was the world's first reusable space vehicle and Columbia was the oldest of a fleet of four and flew her maiden voyage in April 1981.
Her sister ship Challenger exploded soon after take-off 17 years ago killing six astronauts and schoolteacher Christa McAuliffe.
Three days later President Bush led a memorial service to the seven astronauts at the Johnson Space Center in Houston, Texas.
In a statement the families of the astronauts insisted the tragedy should not hamper future space programs.
An independent investigation team spent months studying data recovered from computers tracking Columbia's final moments, and thousands of pieces of recovered debris.
The final conclusions of the Columbia Accident Investigation Board, published in August 2003, confirmed the view that a breach of the shuttle's heat shield on take-off caused it to break up on re-entry.
But it was also highly critical of Nasa itself, saying management blunders were as much to blame as technical problems for the destruction of the shuttle.
It also said that while the space shuttle was not inherently unsafe, a number of mechanical changes should be made in order to ensure safety before flights resume.
It made 29 major recommendations aimed at both a short-term return to space and continuing exploration in the long term.
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