Lady Rothschild, born Serena Mary Dunn, "fought a recent illness most valiantly" and died in hospital in London on Sunday, a spokeswoman said.
Lady Rothschild, who was known to shy away from the public eye, was married to investment banker Lord Jacob Rothschild.
The daughter of Canadian financier Sir James Dunn, she leaves four children and eight grandchildren.
Lady Rothschild, 83, enjoyed a landmark success on the racecourse in 2011, when her colt Nathaniel won the King George VI and Queen Elizabeth Stakes at Ascot.
Having previously claimed the King Edward VII Stakes at the Royal meeting, Nathaniel stepped up to beat 2010 Derby winner Workforce before winning the Coral-Eclipse at Sandown the following season.
Nathaniel clashed on more than one occasion with the great Frankel and ended his career with a third place behind the unbeaten colt in the 2012 Champion Stakes.
However, he became the first of the two to sire a Classic victor when Enable, the current darling of the Flat racing scene and a dual Prix de l'Arc de Triomphe winner, claimed the 2017 Oaks at Epsom.
While Nathaniel was Lady Rothschild's headline horse, she also had an Irish Oaks winner in Great Heavens in her blue and yellow colours, while Pounced was a Breeders' Cup winner for her in America back in 2009.
Lady Rothschild ran Waddesdon Stud in Buckinghamshire and famously paid a then record 4.6 million guineas for a broodmare when purchasing Magical Romance in 2006.
The mare was in foal to Pivotal when going through the ring at Tattersalls, but unfortunately gave birth to her foal in December, compromising her potential on the track.
Fast Results
Scores
