Willard Wigan, whose works are so small they can fit inside the eye of a needle, has dubbed the creation To See or Not to See.
Smaller than a full stop in a newspaper and only viewable with a microscope, the piece took four weeks to complete.
It is on display at the Light House Media Centre in Wolverhampton.
Mr Wigan, who was born in Birmingham, said the work "took every ounce of my skill and took a lot out of me".
More on the micro-Shakespeare and Warwickshire news
"Shakespeare is the greatest storyteller the world has ever known, and as I'm the world's leading micro-sculptor, I wanted to honour him in the best way I can," he said.
"The most difficult aspect was getting his proportions right, but I'm really pleased with the result."
The artist said he created the micro-Shakespeare from synthetic materials, painted using a floating fibre plucked from the air as a brush.
It is surrounded by an 18-carat Elizabethan-style frame with the words "To see or not to see" underneath.
BBC Shakespeare Festival 2016
There will be 30 microscopic pieces on show including "Noddy Holder in a Needle".
Shakespeare, widely regarded as the greatest writer in the English language was born in Stratford-upon-Avon in April 1564 and he died there on April 23, 1616.
An artist famed for his tiny sculptures has created a microscopic William Shakespeare to mark the 400th anniversary of the Bard's death.