In May 1948, Rodgers received a telephone call from Edwin Lester of the Los Angeles Civic Light Opera. Lester had signed former Metropolitan Opera star Ezio Pinza for $25,000 to star in a new show, Mr. Ambassador. The show had not been written, and it never would be. Lester hoped that Rodgers would take over Pinza's contract. Pinza had become bored as the Met's leading lyric bass, and having played the great opera houses, sought other worlds to conquer. Rodgers immediately saw Pinza as perfect for the role of Emile. Lester carefully broached the subject to Pinza and his wife/business manager and provided them with a copy of Tales of the South Pacific. When Pinza read the book, he told Lester, "Sell me right away!" Pinza's contract for South Pacific included a clause limiting his singing to 15 minutes per performance. With Pinza's signing, Rodgers and Hammerstein decided to make his the lead male role, subordinating the story of the pair of young lovers. It was unusual on Broadway for the romantic lead to be an older male.
For the role of Nellie, Rodgers sought Mary Martin, who had nearly been cast to originate the role of Laurey in Oklahoma! Martin was playing the title role in the touring company of Annie Get Your Gun. After Hammerstein and Rodgers saw her play in Los Angeles in mid-1948, they asked her to consider the part. Martin was reluctant to sing opposite Pinza's powerful voice; Rodgers assured her he would see to it the two never sang at the same time, a promise he mostly kept. Rodgers and Martin lived near each other in Connecticut, and after her tour Rodgers invited Martin and her husband, Richard Halliday, to his home to hear the three songs for the musical that he had completed, none of them for Nellie. "Some Enchanted Evening" especially struck Martin, and although disappointed the song was not for her, she agreed to do the part. Although Nellie and Emile were already fully developed characters in Michener's stories, during the creation of South Pacific, Rodgers, Hammerstein and Logan began to adapt the roles specifically to the talents of Martin and Pinza and to tailor the music for their voices.
Martin influenced several of her songs. While showering one day during rehearsals, she came up with the idea for a scene in which she would shampoo her hair onstage. This gave rise to "I'm Gonna Wash That Man Right Outa My Hair". Built around a primitive shower that Logan remembered from his time in the military, the song became one of the most talked-about in South Pacific. To introduce another of Martin's numbers to her, Rodgers called her over to his apartment, where he and Hammerstein played "I'm in Love with a Wonderful Guy" for her. When Martin essayed it for herself, she sang the final 26 words, as intended, with a single breath, and fell off her piano bench. Rodgers gazed down at her, "That's exactly what I want. Never do it differently. We must feel you couldn't squeeze out another sound."
The producers held extensive auditions to fill the other roles. Myron McCormick was cast as Billis; according to Logan, no one else was seriously considered. The two roles which gave the most trouble were those of Cable and Bloody Mary. They tried to get Harold Keel for the role of Cable (he had played Curly in the West End production of Oklahoma!) only to find that he had signed a contract with MGM under the name Howard Keel. William Tabbert was eventually cast as Cable, though Logan instructed him to lose 20 pounds (9.1 kg). African-American singer Juanita Hall was cast as Bloody Mary; Logan recalled that at her audition, she took a squatting pose which proclaimed, "I am Bloody Mary and don't you dare cast anyone else!" Betta St. John, who under the name Betty Striegler had replaced Bambi Linn as Louise in Carousel, took the role of Liat. Logan directed (he and Hayward co-produced with Rodgers and Hammerstein), Mielziner did the stage design, Trude Rittman and Robert Russell Bennett prepared the orchestration, and Elizabeth Montgomery of Motley Theatre Design Group designed the costumes. Salvatore Dell'Isola served as music director.