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Before the film's main title card, a written prologue states, "Appreciation is gratefully acknowledged to the United States Marine Corps and to the Army, the Navy and the Coast Guard whose assistance and participation made this picture possible." Throughout the film, voice-over narration by Reed Hadley as the war correspondent describes the action and gives important dates. The film is based on the best-selling diary of war correspondent Richard Tregaskis, who accompanied the first detachment of Marines to land on Guadalcanal in the Solomon Islands on August 7, 1942. The critical engagement at Guadalcanal was the United States' first victorious offensive action in the South Pacific. According to studio publicity, technical advisor Lt. James W. Hurlbut, who was a war correspondent for the Marine Corps, was at Guadalcanal with Tregaskis. A December 1942 Hollywood Reporter news item noted that "several other companies were in the bidding" for the rights to Tregaskis' book. According to an August 1943 New York Times article, when the studio requested cooperation from the Marine Corps, "one of the first demands was for a rewrite of the script along more accurate lines. Now...the film will follow the book faithfully, departing from it only by centering the story around a single unit of Marines instead of treating the entire action of the campaign in a generalized manner."
The file for Guadalcanal Diary in the Twentieth Century-Fox Produced Scripts Collection, located at the UCLA Arts-Special Collections Library, contains an original story entitled "Marines in the Pacific," submitted to the studio by George Bricker and Herman Ruby. Their work, as well as that of their later collaborator, Leonard Hoffman, does not appear to have been included in the finished film, however. Kenneth Gamet and Waldo Salt worked on versions of the screenplay, according to the studio records, but the extent of their contribution to the completed picture has not been determined. The studio records reveal that technical advisor Capt. Clarence Martin fought at Guadalcanal with the first detachment of Marines.
A April 2, 1943 studio press release announced that Victor McLaglen would play "Father Donnelly" and Preston Foster would play "Capt. Cross." According to a June 15, 1943 Hollywood Reporter news item, however, McLaglen was scheduled to play "Col. Grayson" and was replaced by Minor Watson. No reason for McLaglen's replacement was announced. A May 4, 1943 Hollywood Reporter news item reported that Herbert Evers would make his screen debut in the picture, but his appearance in the released film has not been confirmed. An August 1943 publicity release included George Lynn and Paul Marion in the cast, although their appearance in the completed film has not been confirmed. The same release included Robert Mitchum and Hugh Beaumont in the cast but they could not be identified in the viewed print.
According to the August 1943 studio press release, Anthony Quinn was cast as "Soose Alvarez" after "it was suggested to the producers from an important quarter that it would help the popularity of the United States in Latin American countries if Hollywood would curtail the practices of putting Latins in 'heavy' roles. Furthermore, Quinn greatly resembles Sgt. Frank Few, an Arizona Indian who was one of the great Guadalcanal heroes." The press release further noted that Eddie Acuff's character, "Tex," was based on Gunnery Sgt. Charles E. Angus, a famous Marine rifleman whose marksmanship became part "of the Guadalcanal legend."
Contemporary sources noted that the majority of the film was shot on location at Camp Pendleton, near Oceanside, CA. Many of the Marines stationed there were filmed while on maneuvers and a substantial number appeared in the picture in small speaking parts or as extras. Although a June 24, 1943 Hollywood Reporter news item noted that the studio had obtained waivers from Lloyd Nolan, Preston Foster and William Bendix in order to give only the Marines starring credit in a title card that would read "The United States Marines in Guadalcanal Diary," the Marines did not receive an onscreen credit. Studio publicty noted that the picture was shot for one week aboard a Navy transport. The Hollywood Reporter review related that the demands of Marine Corps officials for authenticity "were met so fully by Hollywood that the re-enacted picture has been added to the official Marine archives in Washington."
According to Hollywood Reporter news items, on November 10, 1943, the film received premieres in Philadelphia, to celebrate the 168th anniversary of the formation of the Marine Corps, and in Hollywood. The Hollywood premiere, which was a benefit for War Charities, was attended by "top-ranking officers of the Marines, Army and Navy," as well as "about fifty war heroes." The sixty-piece Pendleton Field Marine Band played at the event.
The picture marked the screen debuts of stage actor Robert Rose and Richard Jaeckel, who, according to contemporary sources, was a studio messenger boy when he was cast in the production. The film also marked the first time that actor Richard Conte was billed as "Richard." He had previously appeared as Nicholas Conte in the 1939 Twentieth Century-Fox picture Heaven with a Barbed Wire Fence.
On February 28, 1944, Foster, Bendix, Nolan and Jaeckel reprised their roles for the Lux Radio Theatre presentation of Guadalcanal Diary. In a 1946 Saturday Evening Post "The Role I Liked Best" column, William Bendix stated that "Corp. Taxi Potts" was his favorite role because it gave him "the widest range of opportunity" to act. Bendix also related that he and the other actors enjoyed the opportunity to work with the Marines stationed at Camp Pendleton, and that he was touched by the grateful letters he received from servicemen who appreciated his realistic portrayal of a soldier under fire. According to a August 28, 1945 Daily Variety news item, the studio was sued by Donald Peterson for injuries he received during filming. Peterson alleged that he suffered broken ear drums from a premature dynamite explosion and was awarded $15,000 in a jury trial. The studio appealed the decision, however, and the ultimate disposition of the case has not been determined.