The 62-year-old conservationist had been taken to hospital after suffering a serious injury in a fall.
A Clarence House spokesman said: 'It is with deep sadness that we have to confirm that The Duchess of Cornwall's brother, Mark Shand, has today passed away.
"Mr Shand died in hospital as a result of a serious head injury which he sustained during a fall last night.
"The Duchess, The Prince of Wales and all her family members are utterly devastated by this sudden and tragic loss.
"Mark Shand was a man of extraordinary vitality, a tireless campaigner and conservationist whose incredible work through The Elephant Family and beyond remained his focus right up until his death."
The travel writer was in New York for an auction held at Sotheby's in aid of a charity for underprivileged children and the Elephant Family, which aims to save the endangered Asian elephant from extinction in the wild.
It was the finale for the month-long Big Egg Hunt NYC by Faberge, which saw egg sculptures sold to the highest bidder.
The charity event raised 1.6 million US dollars (£950,000) for charity and was also attended by Princess Eugenie, according to reports.
Mr Shand is the chairman of the Elephant Family and is known for his work as a conservationist.
He recently denied being in a relationship Nancy Nancy Dell'Olio, the former girlfriend of ex-England football manager Sven Goran Eriksson.
He said: "Let me be clear, I have never had an affair with Nancy Dell'Olio.
"We have never dated. There is no romance; there has not been any romance, there never will be."
Describing her as a "remarkable character", he explained that he knew Dell'Olio through his charity work.