The 320-page manuscript, which is signed by the composer and contains his handwritten annotations, is expected to fetch £1m-1.5m at auction in May.
Experts at Sotheby’s think that the manuscript could have been used by Rachmaninov to conduct the first ever performance of the symphony in January 1908.
The document may be the last surviving record of the work’s original orchestration, as the composer is likely to have made changes to the score following early performances.
It has not yet been studied in detail, although it is known to feature Rachmaninov’s original revisions and annotations in pencil, ink, and coloured crayons.
Stephen Roe, worldwide head of books and manuscripts at Sotheby's, said: ‘It is a very measured and clearly laid-out score, very neat and to the point. It is a very calculating sort of handwriting.
He continued: ‘There is no substitute for looking at a composer's autograph – you can see various layers of working on it and various layers of realisation of his ideas ... Everything is here, the whole story, the whole great Russian novel that is the second symphony.’
The manuscript had been presumed lost since the 1917 revolution, when Rachmaninov fled St Petersburg with only a small suitcase of belongings. It emerged again in 2004 in the collection of an anonymous European collector.
An attempt to auction it in December 2004 was scuppered by legal challenges from the Rachmaninov estate, which have since been resolved. It passed to the Tabor Foundation, who placed it on permanent loan to the British Library.
The exhibit is now expected to fetch more than double the previous estimate.