Wreath-laying ceremonies were planned for Arlington National Cemetery in Virginia and the Kennedy Space Centre in Florida as NASA commemorated the seven lives lost on January 28, 1986, as well as other deadly space disasters over the years.
"Space exploration is one of the most difficult endeavours we undertake, and from Apollo 1 to Challenger to Columbia, brave Americans have made the ultimate sacrifice in our quest to push new boundaries, and explore new frontiers," President Barack Obama said in a statement marking NASA's annual Day of Remembrance.
"From new partnerships with private industry to the development of groundbreaking inventions that Americans will take with them into the Solar System and eventually to Mars, we will continue our journey of discovery."
Shortly after taking office, Obama cancelled a NASA program to return to the moon, saying he preferred to funnel resources into deep space exploration and aimed to have a human mission to Mars under way by the 2030s.
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The space shuttle programme was formally ended in 2011 after three decades of ferrying astronauts to and from low-Earth orbit.
In the meantime, the world's astronauts hitch rides to the International Space Station aboard Russia's Soyuz capsules, while private companies Boeing and SpaceX ready their own spaceships for use in 2017 and beyond and NASA focuses on building its Orion deep space capsule.
Six NASA astronauts and Christa McAuliffe -- who would have been the first teacher in space -- were killed in the Challenger disaster, when the shuttle exploded 73 seconds after liftoff.
The cause was a failed booster engine, NASA said.
The other major shuttle accident was on February 1, 2003. Seven people died aboard the Columbia shuttle when it broke into pieces while re-entering Earth's atmosphere.