The affair for which Sackville-West is most remembered was with the prominent writer Virginia Woolf in the late 1920s. Woolf wrote one of her most famous novels, Orlando, described by Sackville-West's son Nigel Nicolson as "the longest and most charming love-letter in literature", as a result of this affair.
Unusually, the moment of the conception of Orlando was documented: Woolf writes in her diary on 5 October 1927: "And instantly the usual exciting devices enter my mind: a biography beginning in the year 1500 and continuing to the present day, called Orlando: Vita; only with a change about from one sex to the other" (excerpt from her diary published posthumously by her husband Leonard Woolf).