Chief executive Bill Ruprecht announced the consignment last week. It comes from the estate of Mrs Mellon, who died earlier this year aged 103.
Described as an intensely private woman, Mrs Mellon was the wife of the banking heir and art collector Paul Mellon, with whom she built a formidable collection over decades. Among her achievements was her redesign of the White House rose garden at the request of Jackie Kennedy.
Sotheby's said that the consignment of around 2000 items reflected the five main passions of her life: fashion, horses, art, interior design and gardens.
Proceeds will benefit The Gerard B. Lambert Foundation, a charitable entity supporting horticultural and educational endeavours, established by Mrs Mellon in memory of her father.
Further details of the auction, which is expected to take place in the autumn, will be released at a later date.