In 1951, the novel was adapted into a motion picture of the same name, directed by Zoltan Korda. Paton wrote the screenplay with John Howard Lawson, who was left out of the original credits because he was blacklisted in Hollywood for refusing to give information to the House Un-American Activities Committee (HUAC). Kumalo was played by Canada Lee, Jarvis by Charles Carson, and Msimangu by Sidney Poitier.
In 1983, a historic stage adaptation was performed by the Capital Players theatre group at the Moth Hall in Gaborone, Botswana. The country was at that time one of the leading "frontline states" to apartheid South Africa and a centre for artistic activity that often stood in quiet opposition to the racist regime just across the border. The premiere was attended by Paton himself, who had travelled from Natal, as well as Botswana's then-President Quett Masire (with political acumen, the director had arranged for the first performance to take place on the President's birthday). School students from across the country were bussed to the capital to see the production.
Another film version was released in 1995, directed by Darrell Roodt. James Earl Jones played the Reverend Kumalo and Richard Harris filled the role of Jarvis.
A stage version by the South African playwright Roy Sargeant was developed in early 2003; it was first staged at the National Arts Festival in Grahamstown, Eastern Cape on 27 June 2003 and at the Artscape Theatre in Cape Town on 8 July 2003. The director was Heinrich Reisenhofer. The script, together with notes and activities for school use, was published in 2006 by Oxford University Press Southern Africa.
In 1949, the composer Kurt Weill, in collaboration with the American writer Maxwell Anderson (book and lyrics), composed a musical based on the book called Lost in the Stars. The original Broadway production opened on 30 October 1949 at the Music Box Theatre and starred Todd Duncan and Inez Matthews. It ran for 273 performances before closing on 1 July 1950. It was made into a movie, starring Brock Peters and Melba Moore, released in 1974.
Lost in the Stars is the last work Weill completed before his death in 1950. Although he was influenced by spirituals, jazz and blues, Weill's distinctive and original style shines throughout the score.
Israeli contratenor David D'Or performed in a stage version at the Israeli National Theater ("Habima Theater") in 2004. Maariv in its review wrote: "D'or's outstanding voice is meant for great parts. His voice and presence embraces the audience, who showed their appreciation by a lengthy standing ovation."
In August 2012, the Glimmerglass Opera of New York produced the work, in conjunction with Cape Town Opera, directed by Tazewell Thompson.