"We are saddened by the loss of Sen John Glenn, the first American to orbit Earth. A true American hero. Godspeed, John Glenn," NASA tweeted immediately after his death was announced by the Ohio State University.
Glenn died yesterday at the James Cancer Hospital in Columbus, Ohio, where he was hospitalised for more than a week, the John Glenn College of Public Affairs announced.
The former astronaut had been battling health issues after suffering a stroke a few years ago. He had also undergone a heart valve replacement surgery in 2014.
Glenn, a decorated combat veteran and test pilot who gained worldwide fame as the first American to orbit the Earth, went on to become a US senator and in the autumn of his life returned to space aboard the shuttle Discovery.
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Glenn, who was known for his small-town decency and calm heroics, was the last of the original Mercury 7 astronauts who launched the US space programme. He later served for four terms as a Democratic senator from Ohio.
On February 20, 1962, when Glenn rocketed into space, it was momentous and nerve-racking. Space travel was in its infancy. Every launch and mission captivated the imagination of America.
He made history a second time in 1998, when he returned to space decades later at the age of 77 only to become the oldest person sent into space.
In 1974, he was elected to represent Ohio in the US Senate. Two years later, Glenn's name was among the potential running mates for Democratic presidential nominee Jimmy Carter, but the former US President ended up picking Senator Walter Mondale of Minnesota.
He also campaigned in the Democratic primary for the 1984 presidential election, but ended up losing to Mondale.
He was awarded the Presidential Medal of Freedom, the country's highest civilian honour, in 2012, by President Barack Obama.