As Master of the Mint, Newton was held personally responsible for any debts at the Mint. At his death in 1727, Newton left no will, so his assets were frozen until the Mint was satisfied that the deceased had paid what he "owed" the Crown. The only family member wealthy enough to post bond and release the estate was John Conduitt, who was married to Newton's beloved niece, Catherine Barton. The books in Newton's private library were sold off for £300 to John Huggins, Warden of the Fleet Prison, and given to his son, Charles.

Some time after Charles's death, the books were bought, along with Huggins's house, by the Reverend Dr. James Musgrave. Following Musgrave's death in 1778, the books passed to his family, in whose possession the collection remained more or less intact until 1920. At that time, descendants of the original Musgraves decided to sell the house where the library was kept, and about a thousand volumes that were part of the original sale to Huggins were let go unwittingly for a mere £170. Some of these items resurfaced quickly in the market, but the majority disappeared.

The remaining eight-hundred and fifty-eight were discovered in 1927 at the Wyckeham Musgrave home and offered for sale through the book dealer Sotheran for a sartling £30,000. In 1936 the books remained unsold, and the price fell to £5,000. It was not until 1943 that the Pilgrim Trust paid £5,500 for a lot that included the eight-hundred and fifty-eight volumes, a 1655 edition of Euclid given to Newton by Isaac Barrow (traceable to the original thousand-volume sale), and a Greek Old Testament containing Newtonian annotations. This collection was given to Trinity College, Cambridge. All of those volumes contain original Huggins and Musgrave bookplates as well as a special Trinity bookplate designed by R. A. Maynard. As John Harrison has pointed out in The Library of Isaac Newton (Cambridge, 1978), of those books only eight-hundred and fifty-six could have been from the Newton library, since a few have publication dates after Newton's death.

Over the years, various of the lost thousand volumes have appeared on the antiquarian book market. Remarkably, the Babson Collection includes thirteen volumes known to be from Newton's personal library, all bearing the Huggins and Musgrave bookplates. The Musgrave bookplate has, in most cases, been laid over the Huggins, and is marked with the shelf location for the volume in the Musgrave library at Barnsley Park, Gloucester. While the bookplates cannot be seen as a definitive arbiter of whether or not an item belonged to Newton's library, or whether it is definitely from the original Musgrave sale, they do offer substantial clues to a book's likely provenance.

The second major source of Newton materials was the famous 1936 Sotheby sale of what is known as the Portsmouth Collection. When Conduitt posted bond on the Newton estate, he claimed as a reward all of Newton's unpublished papers, excepting those few deemed fit to publish, which were sent to press and the profit divided. The unpublished papers remained connected to the family estates until 1872, when the fifth Earl of Portsmouth decided to give many of the papers and other items to Cambridge University.

At this time, Newton's own copies of the Principia, with copious annotations and emendations in his hand, about a thousand pages of mathematical notes, the Waste Book (a folio notebook of early scientific and mathematical ideas), and other mathematical manuscripts were given to the University and placed in the University Library. The Portsmouth family retained the papers on chronology, theology, history, alchemy, and the materials for a biography compiled by Conduitt. In 1888, a catalogue of these papers was completed, but the wealth of the collection did not become apparent until the Portsmouth family sent it to auction in the 1930s.

The papers sold by the Portsmouth family form the core of most of the significant collections of Newton manuscripts throughout the world. The economist John Maynard Keynes purchased most of the alchemy manuscripts, as well as almost all of Conduitt's notes, which he subsequently donated to the King's College Library. Lord Wakefield purchased all three-hundred and twenty-nine Mint lots, which he gave to the Mint in London. The majority of the theological manuscripts was purchased by Abraham Yahuda, and later presented to the Jewish National and University Library in Jerusalem.