The classic motor is believed to have been used by the pair to travel around London away from prying eyes during their controversial relationship more than 80 years ago.
Simpson -- who has been described as the Meghan Markle of her day -- won the heart of the future king after they met at a fox-hunting weekend in 1931.
Edward left the throne behind to marry Simpson in June 1937, even though she did not win the approval of the church and the public due to her status as a divorcee.
Now, the 1933 Humber Snipe used to help the burgeoning royal romance blossom is set to go under the hammer this week with an estimate of £20,000-£40,000 ($25,000-$50,000).
Simpson is believed to have covertly traveled around with her beau in the vehicle, which has a small back window "perfect for privacy."
The vehicle belongs to Allan Marshall, 64, from Hull, who is now auctioning off his remarkable motors collected over 60 years due to spiraling maintenance and storage costs.
He said: “I was told the car had been used by Edward and Mrs. Simpson because it was perfect for privacy.
"Thanks to its small back window you couldn’t see who was inside."
The couple first met in 1931 and, by 1934, they were allegedly lovers -- with Prince Edward said to be "besotted" by her.
He liked her domineering manner and abrasive irreverence toward his position. He showered her with money and jewels and in 1935 vacationed with her in Europe.
Edward’s affair with the twice-divorced American led to such grave concerns in British government the couple was followed by the Metropolitan Police Special Branch.
An undated report detailed a visit by the couple to an antique shop, where the proprietor noted "the lady seemed to have POW [Prince of Wales] completely under her thumb."
When King George V died in 1936, Edward ascended the throne as King Edward VIII -- but his reign was short.
His plan to marry Wallis caused a constitutional crisis that led to his abdication that same year.
The royal car will be sold at Hansons Auctioneers in Etwall, Derbys, together with 15 more vintage Humbers, on Sunday, October 25.