The stained tooth was removed in 1940, four years after he married Wallis Simpson, and is expected to fetch £10,000.
It has been kept by his dentist's family until now.
The former king, who was made Duke of Windsor following his abdication in December 1936, had his tooth removed shortly after he was appointed governor of the Bahamas.
The Queen's uncle abdicated after less than a year on the throne to marry his divorcee mistress, the American socialite Wallis Simpson.
The abdication was one of the most difficult periods in the history of the British monarchy.
The former monarch also faced numerous accusations of being a Nazi sympathiser.
His dentist, Dr Hugh Johnson, was later quoted as saying that the duke was "highly strung" and quite "jumpy" while in the operating room.
The dentist also worked on the teeth of Sir Winston Churchill after an accident in New York.
An X-ray and dental card, dated September 9 1940 and signed by Edward Wallis Windsor, will also go under the hammer as part of the same lot.
The tooth is being sold by the grandson of the dentist who carried out the operation.
It will take place at Omega Auctions, the auctioneers who sold one of John Lennon's teeth for £19,000 eight years ago.
Auctioneer Paul Fairweather said: "We expect huge interest in this truly unique item, which is backed up crucially by exceptional provenance.
"Edward's romance and subsequent abdication was one of the more remarkable events in contemporary royal history, and interest in his life remains significant, especially amongst collectors. We're very excited to see what it might achieve."
The Duke Of Windsor died in Paris in 1972, aged 77, and the Duchess of Windsor in 1986.
The tooth is expected to fetch between £5,000 and £10,000 in the sale on September 24.