His final masterpiece will illuminate the external dome of St Paul's Cathedral to celebrate the artist and poet's birthday.
Blake described Ancient Of Days 1827 as "the best I have ever finished".
The artist wanted his work to adorn the walls of churches and public buildings but his dream was not realised during his lifetime.
Martin Myrone, senior curator of pre-1800 British art at Tate Britain, said: "He had a lifelong ambition to see his paintings painted on a large scale....
"It was never going to happen. It was a pipe dream.
"Ancient Of Days is the very last thing he was working on.
"It's the thing he was colouring and painting in the very last days of his life.
"He is said to have stated it is the best thing he has ever done.
"It's an extraordinary work of art."
A projection of the work will be seen on the south side of the dome.
The actual work itself, an illustration for Blake's book Europe A Prophecy, is only 17cm by 23cm.
It shows a long-haired, bearded figure crouching from the heavens.
"It represents an idea of a perhaps rather oppressive, law giving judgmental God," the curator said.
"Blake was a very committed Christian but he had his own interpretation of religion....
"What you see is a realisation of a judging God looming from the heavens."
Blake's birthday is November 28, when he would have been 262 years old.
He died in 1827, aged 69.
His talent was not widely recognised during his lifetime.
Mr Myrone said: "He talked at several points about wanting to produce great public works that would be seen in palaces, public buildings, churches and cathedrals.
"Of course he never had the chance.
"His work is often a few inches high but what Blake wanted to be was a painter of grand pictorial schemes, like Michelangelo and Raphael.
"He imagined himself having a big audience, having lots of people see his art and I think fundamentally that's what he has achieved."
The projection will be visible this weekend.
Tate Britain has collaborated with St Paul's while holding an exhibition of Blake's works.
Dr Paula Gooder, Chancellor of St Paul's Cathedral, said: "This collaboration is made even more special because of the memorial in our crypt to William Blake.
"We hope that the projection of this iconic image will be an inspiration to all who see it."
The projections will run from November 28 to December 1, from 4.30pm to 9pm each evening.
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