Rehearsals began at Broadway's Belasco Theatre on February 2, 1949. There was no formal chorus; each of the nurses and Seabees was given a name, and, in the case of the men, $50 to equip themselves with what clothing they felt their characters would wear from the military surplus shops which lined West 42nd Street. Don Fellows, the first Lt. Buzz Adams, drew on his wartime experience as a Marine to purchase a non-regulation baseball cap and black ankle boots. Martin and Pinza had not known each other, but they soon formed a strong friendship. Of the mood backstage, "everyone agreed: throughout the rehearsals Logan was fiery, demanding, and brilliantly inventive." He implemented lap changes (pioneered by Rodgers and Hammerstein in Allegro), whereby the actors coming on next would already be on a darkened part of the stage as one scene concluded. This allowed the musical to continue without interruption by scene changes, making the action almost seamless. He soon had the Seabees pacing back and forth like caged animals during "There Is Nothing Like a Dame", a staging so effective it was never changed during the run of the show. One Logan innovation that Rodgers and Hammerstein reluctantly accepted was to have Cable remove his shirt during the blackout after he and Liat passionately embrace on first meeting, his partial nakedness symbolizing their lovemaking. As originally planned, Martin was supposed to conclude "I'm in Love with a Wonderful Guy" with an exuberant cartwheel across the stage. This was eliminated after she vaulted into the orchestra pit, knocking out Rittman.
There were no major difficulties during the four weeks of rehearsal in New York; Martin later remembered that the "gypsy run-through" for friends and professional associates on a bare stage was met with some of the most enthusiastic applause she could remember. One of the few people having trouble was Pinza, who had difficulty adjusting to the constant alterations in the show – he was used to the operatic world, where a role rarely changed once learned. Pinza's mispronunciations of English exasperated Logan, and driving to New Haven for the first week of previews, Pinza discussed with his wife the possibility of a return to the Met, where he knew audiences would welcome him. She told him to let South Pacific 's attendees decide for themselves. When the tryouts began in New Haven on March 7, the play was an immediate hit; the New Haven Register wrote, "South Pacific should make history".
Nevertheless, a number of changes were made in New Haven and in the subsequent two weeks of previews in Boston. The show was running long; Logan persuaded his friend, playwright Emlyn Williams, to go over the script and cut extraneous dialogue. There were wide expectations of a hit; producer Mike Todd came backstage and advised that the show not be taken to New York "because it's too damned good for them". The show moved to Boston, where it was so successful that playwright George S. Kaufman joked that people lining up there at the Shubert Theatre "don't actually want anything ... They just want to push money under the doors."
South Pacific opened on Broadway on April 7, 1949, at the Majestic Theatre. The advance sale was $400,000, and an additional $700,000 in sales was made soon after the opening. The first night audience was packed with important Broadway, business, and arts leaders. The audience repeatedly stopped the show with extended applause, which was sustained at length at the final curtain. Rodgers and Hammerstein had preferred, in the past, not to sponsor an afterparty, but they rented the St. Regis Hotel's roof and ordered 200 copies of The New York Times in the anticipation of a hit. Times critic Brooks Atkinson gave the show a rave review.
Three days after the opening, Pinza signed a contract with MGM to star in films once his obligation to appear in the show expired. He left the show June 1, 1950, replaced by Ray Middleton, though Pinza missed a number of shows due to illness before that. Martin recalled that, unused to performing eight shows a week, the former opera star would sing full out early in the week, leaving himself little voice towards the end, and would have his understudy go on. Nevertheless, during the year he was in the show, and although aged 58, he was acclaimed as a sex symbol; George Jean Nathan wrote that "Pinza has taken the place of Hot Springs, Saratoga, and hormone injections for all the other old boys".
A national tour began in Cleveland, Ohio, in April 1950; it ran for five years and starred Richard Eastham as Emile, Janet Blair as Nellie and Ray Walston as Billis, a role Walston would reprise in London and in the 1958 film. For the 48,000 tickets available in Cleveland, 250,000 requests were submitted, causing the box office to close for three weeks to process them. Jeanne Bal and Iva Withers were later Nellies on this tour. A scaled-down version toured military bases in Korea in 1951; by the request of Hammerstein and Rodgers, officers and enlisted soldiers sat together to view it.
Martin left the Broadway production in 1951 to appear in the original London West End production; Martha Wright replaced her. Despite the departure of both original stars, the show remained a huge attraction in New York. Cloris Leachman also played Nellie during the New York run; George Britton was among the later Emiles. The London production ran from November 1, 1951 for 802 performances at the Theatre Royal, Drury Lane. Logan directed; Martin and Wilbur Evans starred, with Walston as Billis, Muriel Smith as Bloody Mary and Ivor Emmanuel in the small role of Sgt. Johnson. Sean Connery and Martin's son Larry Hagman, both at the start of their careers, played Seabees in the London production; Julie Wilson eventually replaced Martin. On January 31, 1952, King George VI attended the production with his daughter Princess Elizabeth and other members of the Royal Family. He died less than a week later.
The Broadway production transferred to the Broadway Theatre in June 1953 to accommodate Rodgers and Hammerstein's new show, Me and Juliet, although South Pacific had to be moved to Boston for five weeks because of schedule conflicts. When it closed on January 16, 1954, after 1,925 performances, it was the second-longest-running musical in Broadway history, after Oklahoma!. At the final performance, Myron McCormick, the only cast member remaining from the opening, led the performers and audience in "Auld Lang Syne"; the curtain did not fall but remained raised as the audience left the theatre.