There are many film versions of the story, the two most widely known being Jean de Limur's 1929 version made by Paramount Pictures and starring Jeanne Eagels, and William Wyler's 1940 version made by Warner Bros. and starring Bette Davis. While de Limur's English-language version was made at Paramount's Astoria studios, several foreign-language versions were produced at the company's studios in Joinville-le-Pont: Louis Mercanton's French version, La lettre (1930), Dimitri Buchowetzki's German version, Weib im Dschungel (1931), Adelqui Migliar's Spanish version, La carta (1931) and Jack Salvatori's Italian version, La donna bianca (1931). Another non-English-language adaptation is Kira Muratova's Перемена участи / Peremena uchasti / A Change of Fate (1987).
The story was also adapted for four television anthology series: on November 3, 1952 for Broadway Television Theatre with Sylvia Sidney; on October 15, 1956 for Producers' Showcase (directed by William Wyler), in 1960 for The Somerset Maugham Hour and in 1969 for W. Somerset Maugham (directed by Christopher Morahan). A made-for-TV movie directed by John Erman and starring Lee Remick was made and released in 1982 for ABC.
Clark Gesner adapted The Letter into a musical called The Bloomers in 2000.
The Santa Fe Opera commissioned composer Paul Moravec and librettist Terry Teachout to write an operatic version. It received its premiere performance on 25 July 2009 in a production directed by Jonathan Kent and starring soprano Patricia Racette as Leslie Crosby.