The perfect, classic emerald-cut D colour diamond was purchased by an anonymous buyer via a telephone bid.
It had a pre-sale estimate of $19 million to $25 million.
The diamond is about the size of a walnut and was mined by De Beers in Southern Africa.
Originally weighing over 200 carats, its owner spent more than a year perfecting its cut and polish.
Gary Schuler, the head of Sotheby’s jewellery department in New York, said the gem was the definition of perfection.
“The colour is whiter than white, it is free of any internal imperfections, and so transparent that I can only compare it to a pool of water,” he said.
Mr Schuler said the distinguishing characteristic of the huge diamond was its size and beautiful shape.
The diamond was the top-selling item in a sale of more than 350 jewels that were expected to sell for a total of more than $50 million.
The $22.1 million price, which includes the buyer’s premium, fell short of the $30.6 million world record price paid for a 118.28-carat white diamond in Hong Kong in 2013.
A flawless pink diamond, dubbed the Pink Star, set a world record price for a gemstone at auction when it sold for $83.02 million in Geneva in 2013.
Sotheby’s said that from 1990 to 2013 the price per carat for a 100-carat perfect diamond had risen from $125,000 to $260,000.
Other auction highlights included a pear-shaped, purplish-pink diamond weighing 6.24 carats and a blue diamond ring weighing 6.06 carats.