The title had been used before by Warner Brothers for a 1926 silent adventure film by the same name starring Monte Blue, who also has a small role in this film. However, the plots of the two films bear no resemblance to each other.
Initially, it was planned that the film would portray an attempt to avert a Japanese plan to bomb Pearl Harbor. When the real-life Pearl Harbor bombing occurred, the script was quickly rewritten to change the location of the planned attack to Panama. The title however remained the same, even though the Pacific is never seen, let alone crossed.
Director John Huston was called up to military service during filming; he claimed he left at the point near the end of the film in which Bogart is trapped in a house at gun-point. Vincent Sherman finished directing the film, minus the script which Huston took with him, explaining "Bogie will know how to get out". An implausible escape and plot wrap-up was shot, which Huston declared "lacked credibility".
On board, he meets Canadian Alberta Marlow (Mary Astor) and Dr. Lorenz (Sydney Greenstreet), a professor of sociology who makes no secret of his admiration of the Japanese and is thus not popular in the Philippines, where he resides. Leland, in his turn, makes it clear to Lorenz that he has no loyalty toward his country and would fight for anyone willing to pay him.
During a stop in New York, Leland reports to Colonel Hart (Paul Stanton), an undercover intelligence officer. Lorenz is a known enemy spy, but Hart and Leland are uncertain about Marlow. Upon returning to the ship, Leland surprises a Filipino man (Rudy Robles) who is about to shoot Lorenz, thus gaining Lorenz's confidence. Second-generation Japanese-American Joe Totsuiko (Victor Sen Yung) embarks as a passenger.
As they arrive in Panama, the captain announces that the ship has been denied passage through the strategically vital canal and will be forced to take a long detour around Cape Horn. Leland, Marlow and Lorenz disembark to wait for another ship. Several crates are unloaded addressed to a Dan Morton at the Bountiful plantation.
Lorenz asks Leland, who was once stationed in the area, to procure up-to-date schedules for the American planes that patrol the canal. Leland meets with his local contact, A.V. Smith (Charles Halton), and convinces him to provide the real schedules, as Lorenz could easily find out if he were given fake ones. The date is December 6, 1941 - the eve of the attack on Pearl Harbor.
Having delivered the schedules after haggling with Lorenz over their price, Leland is knocked out. He wakes up several hours later and finds out that both Lorenz and Marlow have left the hotel. He immediately calls Smith and warns him to change the patrol schedule, then heads out to the Bountiful plantation, where he sees a torpedo bomber being prepared. He is caught, however, and brought inside to Lorenz, Marlow, and Totsuiko.
Marlow turns out to be the daughter of the plantation's owner, Dan Morton (Monte Blue), a drunk whose weakness is being exploited by the spy ring to provide a base for its activities. To Leland's relief, Marlow's only stake in the affair is concern for her father.
Lorenz reveals that they killed Smith before he could have the schedule changed and that they are planning to torpedo the Panama Canal Locks. At the last minute, Leland overpowers Totsuiko (Marlow's father is killed in the process). Leland takes over a machine gun and shoots down the bomber aircraft, piloted by no less than an Imperial Japanese prince, as it tries to take off. Leland dispatches Lorenz's men in the ensuing firefight. At the end, a defeated Lorenz tries to commit seppuku, but his nerve fails him and he begs Leland to shoot him. Leland refuses, as Lorenz has "a date with Army intelligence".